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AYURGENOMICS: A NEW APPROACH IN PERSONALIZED AND PREVENTIVE MEDICINE

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Genomics has ushered in an era of predictive, preventive and personalized medicine wherein it is hoped that not too far in the future there would be a paradigm shift in the practice of medicine from a generalized symptomatic approach to an individualized approach based on his or her genetic makeup. Several approaches are being attempted to identify genetic variations that are responsible for susceptibility to diseases and differential response to drugs, however, have met with only a limited success. Ayurveda, an ancient Indian system of medicine documented and practiced in India since 1500 B.C has personalized approach towards management of health and disease. According to this system, every individual is born with his or her own basic constitution, termed Prakriti which to a great extent determines inter individual variability in susceptibility to diseases and response to external environment, diet and drugs. This system is in contrast to contemporary medicine, where a preventive and curative regime can be adopted only after an individual suffers or shows signs of an impending illness and there are no methods to identify healthy individuals who would be differently susceptible to disease. We thought an integration of Ayurveda and genomics if attempted in a systematic manner which we call as Ayurgenomics could help fill the gap. In an exploratory study we have provided evidence that healthy individuals of contrasting Prakriti types i.e. Vata, Pitta and Kapha identified on the basis of Ayurveda exhibit striking differences at the biochemical and genome-wide gene expression level. Subsequently, we could also demonstrate that these differences are meaningful since we could follow one of the cues from gene expression differences and identify a genetic marker that is associated high altitude adaptation and a high altitude illness. Our studies have provided a novel molecular framework for integration of these two disciplines for predictive and personalized medicine. Correspondence to Mitali Mukerji (mitali@igib.res.in) Phone 91-11-27666156, Fax 91-11-27667471 and Bhavana Prasher (bhavana@csir.res.in) 91-11-23710158, Fax 91-11-23736842 T here has been a steady rise in prevalence of common diseases like diabetes, asthma, cardiovascular disorders, epilepsy, stroke, schizophrenia and bipolar disorder in the world. These have been mainly attributed to changes in life styles and dietary habits as well as inability to adapt to new habitats and environments. Nearly 1% of the world population suffers from these diseases and in some cases like diabetes and obesity, the numbers are considerably higher and also dangerously on the rise. With the steady increase in average life expectancy of humans, this has become a major concern since most of these common diseases extend throughout life and require long-term medication often associated with added complications and/or expensive interventions. Identifying factors that predispose individuals to these diseases and predict their progression as well as designing customized drug regime for each individual to minimize side-effects is a major challenge.
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10 SCIENCE AND CULTURE, JANUARY-FEBRUARY, 2011
AYURGENOMICS: A NEW APPROACH IN PERSONALIZED AND
PREVENTIVE MEDICINE
MITALI MUKERJI
1
AND BHAVANA PR ASHER
2
Genomics has ushered in an era of predictive, preventive and personalized medicine wherein it is
hoped that not too far in the future there would be a paradigm shift in the practice of medicine
from a generalized symptomatic approach to an individualized approach based on his or her
genetic makeup. Several approaches are being attempted to identify genetic variations that are
responsible for susceptibility to diseases and differential response to drugs, however, have met
with only a limited success. Ayurveda, an ancient Indian system of medicine documented and
practiced in India since 1500 B.C has personalized approach towards management of health and
disease. According to this system, every individual is born with his or her own basic constitution,
termed Prakriti which to a great extent determines inter individual variability in susceptibility to
diseases and response to external environment, diet and drugs. This system is in contrast to
contemporary medicine, where a preventive and curative regime can be adopted only after an
individual suffers or shows signs of an impending illness and there are no methods to identify
healthy individuals who would be differently susceptible to disease. We thought an integration of
Ayurveda and genomics if attempted in a systematic manner which we call as Ayurgenomics could
help fill the gap. In an exploratory study we have provided evidence that healthy individuals of
contrasting Prakriti types i.e. Vata, Pitta and Kapha identified on the basis of Ayurveda exhibit
striking differences at the biochemical and genome-wide gene expression level. Subsequently, we
could also demonstrate that these differences are meaningful since we could follow one of the
cues from gene expression differences and identify a genetic marker that is associated high altitude
adaptation and a high altitude illness. Our studies have provided a novel molecular framework
for integration of these two disciplines for predictive and personalized medicine.
ARTICLE
1
Genomics and Molecular Medicine, Institute of Genomics
and Integrative Biology, (IGIB) CSIR, Mall Road, New Delhi,
110007, India.
2
Planning and Performance Division, Council of Scientific
and Industrial Research, Anusandhan Bhawan, 2, Rafi Marg,
New Delhi, 110001, India
Correspondence to Mitali Mukerji (mitali@igib.res.in) Phone
91-11-27666156, Fax 91-11-27667471 and Bhavana Prasher
(bhavana@csir.res.in) 91-11-23710158, Fax 91-11-23736842
T
here has been a steady rise in prevalence of common
diseases like diabetes, asthma, cardiovascular
disorders, epilepsy, stroke, schizophrenia and bipolar
disorder in the world. These have been mainly attributed
to changes in life styles and dietary habits as well as
inability to adapt to new habitats and environments. Nearly
1% of the world population suffers from these diseases
and in some cases like diabetes and obesity, the numbers
are considerably higher and also dangerously on the rise.
With the steady increase in average life expectancy of
humans, this has become a major concern since most of
these common diseases extend throughout life and require
long-term medication often associated with added
complications and/or expensive interventions. Identifying
factors that predispose individuals to these diseases and
predict their progression as well as designing customized
drug regime for each individual to minimize side-effects is
a major challenge.
It is now well acknowledged that a large number of
diseases are inherited in the families. With the discovery
of the double helical structure of DNA and subsequent
advancements in the field of molecular biology and
genetics, the cause of pathogenesis in many of these
VOL. 77, NOS. 1–2 11
diseases has been traced to changes in the DNA from
one individual to another. The human genome, that is the
entire genetic content, is composed of 23 chromosome
pairs (diploid) where each set (haploid) has 3 billion base
pairs of DNA inherited from either of the parents. There
are large numbers of variations in the human genome
sequence which are called Single Nucleotide
Polymorphisms (SNP). Some of these variations are present
in large number of individuals and are called as common
variations and some are rare. If the variations are present
in less than 1% of the population they are mostly classified
as mutations. Many rare diseases like hemophilia, beta-
thallasemia etc. are monogenic, caused due to mutations
in single genes. Most of the common diseases such as
diabetes, asthma, cardiovascular disease and so on are
multigenic complex disorders involving many genes. It is
generally observed that common diseases are a
consequence of cumulative effect of a large number of
variations in the genome which independently have small
effects that are not sufficient to cause the disease.
However, it is now being increasingly realized that even
those diseases that were considered to be monogenic
sometimes exhibit differences in manifestation of disease
in different individuals in spite of carrying the same
mutations. This is thought to be due to presence of
variations in other genes that could modify the effect of
the primary mutation. Further there is a complex interplay
of gene and environment involved in most of the diseases.
For example, in cardiovascular disease (CVD), various
parameters like blood pressure, levels of lipoproteins (HDL
and LDL), triglycerides and total cholesterol in the blood
along with life style habits such as diet, smoking and lack
of exercise, stress etc have been identified as risk factors
in these diseases. Each of these parameters can be
modulated by a large number of genes. Thus an
astronomical number of possibilities of combination of
variants from different genes and environment could
contribute not only to differences in clinical manifestation
of disease but also to the variability in age of onset,
severity and symptoms of the diseases. Another aspect of
the disease is the drug dosage management. Most of
these diseases require long term drug administration and
there is a high variability in individual response to drug
dosage and adverse effects due mainly to variations in
the genes responsible for drug transport and drug
metabolism within the individual’s system. Therefore design
of optimum dosage with least side-effects is difficult to
establish. Thus an important starting point in
understanding the factors responsible for these diseases
and how the treatment regime can differ from individual to
individual, is to study the prototype sequence of a human
genome that could be used as a reference for comparison
between healthy and affected individuals. With the
availability of the complete sequence of the human genome,
it is now possible to entertain the thought that not too far
in the future, each individual would have a personalized
health regime based on his/her genetic make-up.
The first draft of the Human Genome sequence made
available in 2001, came with its own share of surprises,
the most striking amongst them was that we did not have
“The Human Genome Sequence” as mentioned above
1,2
.
Two unrelated humans differ on an average one nucleotide
every 1000 base pairs. If we extend that to the entire
genome (haploid size 3x10
9
base pairs) these would
translate to over 6 million differences between any two
individuals. This makes it nearly impossible to reconstruct
a unique prototype sequence of 3 billion nucleotides which
we could refer as “The Human Genome Sequence”. Re-
sequencing of entire genomes in the recent times of a
couple of prominent humans has further confirmed that
there are extensive differences between individuals not
only with respect to single nucleotides (i.e. SNP) but also
large scale gain and loss of chromosomal segments due
to genome rearrangements. Discovering meaningful
variations (between the healthy and affected) from this
vast pool of common variations (between two healthy) is
now an insurmountable challenge.
The observed variability in the human genome
sequence led to a natural progression to an International
HapMap Consortium project
3,4
. This project was
undertaken to catalog all human genome variations and to
infer patterns of variations across global populations. The
project was primarily aimed at speeding the discovery of
genes related to common illnesses through capturing extent
of genome-wide diversity across 269 individuals from
Caucasian, Chinese, Japanese and Yoruban populations.
These efforts have uncovered nearly 11 million SNPs in
the human genome wherein nearly 4.2 million SNPs have
frequency higher than 1% in all the major populations.
Though all the variations may not be functional, these
variations could act as landmarks and a combination of
these landmarks (defined as haplotypes) can define
uniqueness of genomes of different individuals/populations.
It is generally seen that specific mutations mostly arise
once in the population and spread with the subsequent
growth of the population and are introduced in different
populations due to migrations and subsequent admixture.
If a mutation arises in a specific haplotype background
(that can be defined by a combination of SNP landmarks)
the frequency of this haplotype would differ between the
cases (diseased individuals) and controls (healthy
12 SCIENCE AND CULTURE, JANUARY-FEBRUARY, 2011
individuals). Once these haplotype backgrounds are
identified the causal mutation can be traced relatively easily
through sequencing the regions demarcated by the
landmarks (haplotypes). This is similar to reaching a
destination following a combination of landmarks wherein
each landmark per se might not be so informative. The
haplotype information generated in the HapMap data for
different populations can be used for identification of
mutations through comparison of frequencies between
controls and cases. Based on the differences in frequencies
of these haplotypes between affected and unaffected
individuals an ODDs ratio can be calculated for that
haplotype to be associated with the disease. Therefore it
was anticipated that this basal variation data would be
useful for not only improved understanding of disease
etiology, mechanism and discovery of new drug targets
but would provide predictive marker for disease risk
assessment, prevention, progression as well as differential
drug response and side effects.
Since most of the genes in complex disorders are
undiscovered, it has been presumed that an unbiased and
exploratory approach which could compare genome-wide
variations between cases and controls through comparison
of variations at genome wide scale could reveal causal
haplotypes. With advancement in genomic technologies
it has become possible to interrogate the entire genome-
wide variations of an individual in one single experiment.
This led to studies called as “Genome Wide Association
Studies (GWAS) “ where variations in its entirety for many
diseased and healthy subjects could be compared to
identify regions that had sufficiently different frequency
and could be associated with the disease
5
. Once these
regions are identified one could look at the genes and
start to make sense of the underlying biology of the
disease. These experiments have provided valuable insights
into genetic underpinnings of diseases and also seemingly
unrelated diseases are getting linked through common set
of genes and pathways identified through these studies.
Although in these experiments many disease gene
associations were observed but with very less ODDs ratio
that was predicted to confer only slightly higher risk to
the diseased population as compared to controls. As these
studies were carried out in large number of individuals,
the power of the study was adequate however, the
inferences were inadequate
6
. In most of these studies the
cases and controls are chosen from the same ethnicity,
gender and age to remove the effect of any of these factors
on the disease condition. These studies have been highly
dependent on strong contrasts in disease susceptibility
between cases and controls. Controls do not have obvious
clinical disease and in general comprise of a heterogeneous
set of individuals who are differently predisposed or
protected from diseases. It is being increasingly realized
that identification of sub-groups within normal controls
corresponding to contrasting disease susceptibility is likely
to lead to more effective discovery of predictive markers
for diseases. There are however no modern methods
available to look at inter-individual differences within
ethnically matched healthy populations. We, at the Institute
of Genomics and Integrative Biology, have been exploring
the concept whether Ayurveda, an ancient Indian system
of predictive and personalized medicine, can fill this gap
and help in identification of predictive markers for some
of these complex diseases. This integrated field of research
which has been initiated since 2001.
Ayurveda, an ancient Indian system of Medicine that
has been documented and practiced since 1500 B.C. is a
living tradition of healthcare even today. This can be
judged by the fact that nearly 65% of India uses traditional
medicine with its growing acceptance as an alternative
medicine in many parts of the world. Ayurveda has
personalized approach in predictive, preventive and
curative aspects of medicine. It deals with inter-individual
variability in assessing susceptibility, establishing
diagnosis, and prognosis mainly on the basis of
constitution type of the individual (“Prakriti”). selection
of a suitable dietary, therapeutic and life style regime is
made on the basis of clinical assessment of the individual
keeping one’s Prakriti in mind
7-10
. This is in contrast with
modern medicine wherein assessing susceptibility might
be based on genetic markers, diagnosis based on objective
parameters, dietary and life style recommendation are
disease based and treatment is mostly symptomatic with
the dosage management mostly empirical. Though many
sophisticated and state-of-the-art methods are available,
there is minimal cross-talk among any of these steps
mentioned above. We felt it important to explore whether
the ancient and documented system of constitution types
described in Ayurveda could be correlated with modern
biology (Figure 1).
Prakriti is a consequence of the relative proportion
of three entities (Tri-Doshas), Vata (V), Pitta (P) and Kapha
(K), which are not only genetically determined (Shukra
Shonita), but also influenced by environment (Mahabhuta
Vikara), especially maternal diet and lifestyle (Matur Ahara
Vihara), and age of the transmitting parents (Kala -
Garbhashaya). The ethnicity, familial characteristics as well
as place of origin of an individual are also described to
influence development of Prakriti besides the afore-
mentioned individual specific factors. The Prakriti of an
individual is fixed at the time of birth and remains invariant
VOL. 77, NOS. 1–2 13
throughout the lifetime. In an individual, the tri-doshas
work in conjunction and maintain homeostasis throughout
the lifetime starting from fertilization. Distinct properties
and functions have been ascribed to each Dosha. The
kinetic components of a system have been ascribed to
Vata, the metabolic components to Pitta and the structural
and stability components to Kapha. For instance, Vata
contributes to manifestation of shape, cell division,
signaling, movement, excretion of wastes, cognition and
also regulates the activities of Kapha and Pitta. Kapha is
responsible for growth and maintenance of structure,
storage and stability. Pitta is primarily responsible for
metabolism, thermo-regulation, energy homeostasis,
pigmentation, vision, and host surveillance. Hence the
differences in Tridoshic proportions right from the time of
fertilization are manifested as different phenotypes that can
be with respect to external appearances, body physiology,
and response to external environment etc. Thus a
continuum of relative proportions of Doshas results in
seven possible constitutional types namely Vata, Pitta,
Kapha, Vata-Pitta, Pitta-Kapha, Vata-Kapha and Vata-Pitta-
Kapha. Amongst these, the first three are considered as
extremes, exhibiting readily recognizable phenotypes that
are evident not only at the anatomical and physiological
level but also at the level of mental aptitude. However, the
individuals of such predominant Vata, Pitta, Kapha Prakriti
are relatively infrequent in the population. At the
anatomical level these constitution types differ with respect
to body frame and build, skin, eye and hair colour texture
and composition; at the physiological level the differences
are exhibited with respect to
food and bowel habits,
tendency to gain weight,
disease resistance and
healing capacity, tolerance for
specific weather, metabolism
of toxic compounds etc.
Besides these constitution
types have specific likes,
dislikes and suitability of
tastes and there are
differences in memory
retention as well as aptitude
differences (see Table).
The constitution type
and Prakriti levels of dosha
are considered as normal for
that individual. Any
perturbation from an
individual’s homeostatic state
of Doshas leads to diseases. Elevation of Vata, Pitta Kapha
beyond an individual’s threshold leads to manifestation of
specific doshic disorders. Amongst the Vatic disorders
developmental, neurological, dementia, movement and
speech disorders, arrhythmias etc are described. In Pitta
elevation, ulcer, bleeding disorders, skin diseases etc. and
in Kapha obesity, diabetes, atherosclerotic conditions etc.
are described. The perturbation of specific doshas in an
individual is assessed through the symptoms and the aim
of the Ayurveda physicians is to measure the amount of
perturbation and bring back the doshas to his or her
homeostatic state by appropriate dietary and therapeutic
regime. Each of the food or medicine including lifestyle
related things have been described to enhance or reduce
a particular doshic state and therefore an individual-
specific customized treatment is provided. Thus the beauty
of Ayurveda lies in the fact that an individual, a disease
condition, drug, diet as well as environment is described
in terms of doshic components and appropriate
customizations can be provided to balance these states.
From the foregoing description it is evident that
tridoshas and Prakriti are the important basis of
personalized tenets of Ayurveda for application in
predictive medicine, it is imperative to establish their
molecular basis. We felt that since Doshas are also
explained to be elicited differently in different constitution
types, it might be worthwhile to use modern genomic
approaches to get a molecular explanation of the Tridosha
concept by studying individuals who have predominance
of the Doshas. Our basic working hypothesis was that if
Figure 1. Proof of concept of the study
14 SCIENCE AND CULTURE, JANUARY-FEBRUARY, 2011
Ayurveda describes Vata to be the kinetic component,
Kapha as a structural component and Pitta as a metabolic
component, do individuals of different constitution types
who are explained to be Vata, Pitta or Kapha types express
different set of genes that governs these processes?
(Figure 2) If this were to happen then one could identify
such genes and take it further to see whether these genes
confer differences in susceptibility to diseases or
differences in drug responsiveness. Differences in HLA
gene polymorphism between Prakriti group has been
described earlier
11
. No studies at the genome-wide scale
have however been attempted.
We adopted the Ayurvedic method of Prakriti
analysis and identified normal healthy individuals belonging
to the three extreme and contrasting Prakriti groups -
Vata, Pitta, Kapha. In order to rule out effect of ethnicity
related genetic variation confounding our study we carried
out our Ayurveda study on individuals primarily of Indo-
European origin (Figure 3). Our studies have shown that
normal healthy individuals from the three most contrasting
constitution types exhibit striking differences at the genome
wide expression levels and biochemical and hematocrit
parameters measured using peripheral blood
12
. For instance
lipid profiles, uric acid, haemoglobin, blood clotting time
serum zinc levels etc varied from one group to the other.
At the expression level we also observed enrichment in
core biological processes like transport, immune response,
blood coagulation etc. There were correlations among
biochemical profiles, functional categories of differentially
expressed genes and the Ayurvedic descriptions as well.
We observed higher levels of markers of metabolic
syndrome and chronic inflammation (TG, total cholesterol,
LDL, VLDL, High LDL/HDL, low HDL, uric acid, SGPT) in
Kapha males compared to Vata and this was also consistent
with over-expression of genes involved in inflammatory
response in these individuals. Prothrombin time, indicative
of blood coagulation process, was observed to be low in
TABLE: Distinguishing features of three contrasting Prakriti types Vata, Pitta and Kapha and their disease
predisposition as described in the original text.
S.No Features Vata Pitta Kapha
1 Body frame Thin Medium Broad
2 Body build and musculature Weakly developed Moderate Well developed
3 Skin Dry and cracked Soft, thin, with tendency for Smooth and firm, clear
moles, acne and freckles complexion
4 Hair Dry, thin, prone to breaks Thin, oily, early graying Thick, smooth and firm
5 Weight gain Recalcitrant Fluctuating Tendency to obesity
6 Food and bowel habits Frequent, variable and higher capacity for food and Low digestive capacity and
irregular water consumption stable food habits
7 Movements and physical Excessive and brisk Less mobile
activities
8 Tolerance for seasonal Cold intolerant Heat intolerant Endurance for both
weather
9 Disease resistance and Poor Good Excellent
healing capacity
10 Metabolism of toxic Moderate Quick Poor
substances
11 Communication Talkative Sharp, incisive communication Less vocal with good
with analytical abilities communication skills
12 Initiation capabilities Quick, responsive and Moderate, upon conviction Slow to initiate new things
enthusiastic and understanding
13 Memory Quick at grasping and Moderate grasping and Slow grasping and Good at
poor retention retention retention
14 Ageing Fast Moderate Slow
15 Disease Predisposition/ Developmental, Neurological, Ulcer, bleeding disorders, Obesity, diabetes,
Poor prognosis dementia, movement and Skin diseases atherosclerotic conditions
speech disorders, Arrhythmias
VOL. 77, NOS. 1–2 15
Kapha males. Further, higher levels of expression of
haemoglobin genes in Pitta compared to Vata and Kapha
also corroborates with the differences in haemoglobin levels
between the Prakritis and correlates with the redness of
skin as a phenotype in Pitta individuals. Ayurveda
proposes that the proportions of Doshas are restrained
within allowable limits and disease is a consequence of
perturbation from the
threshold. 30% of the entire
data set of the genes that
were differentially expressed
among Prakriti groups were
reported to be associated
with complex and
monogenic diseases. There
were a significant number of
hub genes (these genes
interact with more than ten
genes) which link complex
diseases related to
diabetes, immunological,
infectious, cardiovascular,
neuro-psychiatric disorders
and cancer. Ayurveda based
method of Prakriti
classification thus allowed
us for the first time to
identify biochemical and
expression differences
amongst normal healthy individuals. We reasoned that
identification of genetic variations which can be correlated
to Prakriti phenotypes would facilitate predictive marker
discovery.In order to test this hypothesis we studied
genetic differences between a set of genes that were
observed to be differentially expressed. To our surprise
we observed significant differences in frequency of
Figure 3. Genotype-Phenotype Correlation Based on the Principles of Ayurveda With Special Focus on Prakriti.
Figure 2. Working hypothesis of the study.
16 SCIENCE AND CULTURE, JANUARY-FEBRUARY, 2011
variations of a few of these genes among the three
contrasting constitution types. Most importantly if all the
individuals of contrasting constitution types were pooled
together, the frequency of these genetic variations
assumed an average value which was similar to that of
the population of the same ethnic background. This
highlights the importance of this method which allowed
us to partition the common variations in some of the genes
even within genetically homogeneous population. Since
these constitution types are described to be differently
predisposed to diseases, we ask the question, could these
markers that were partitioned according to constitution
types also serve as markers for differential predisposition?
In order to test this further we followed a gene EGLN1
which is a key oxygen sensor that can switch on a subset
of genes when required that allows a body to adapt to
low oxygen conditions. In our dataset this gene differed
both with respect to its expression level as well as at
genetic level between Pitta and Kapha constitution types,
and the expression differences were coretable to genetic
variations. We therefore reasoned if these variations could
be involved in the response of an individual to high oxygen
or low oxygen conditions. One of the physiological
conditions where oxygen levels are low is at high altitudes
to which natives get acclimatized and often un-acclimated
sojourners suffer from High Altitude Pulmonary Edema
(HAPE). High altitude region, according to Ayurveda is
considered as Kapha-Vata predominant region where
disorders of a Kapha-Vata are more prevalent and Pitta
was anticipated to have higher adaptive capacity. To our
amazement we actually observed the Pitta genotype to be
highly represented in natives of high altitude and that of
the Kapha genotype in those individuals who develop
HAPE. In order to substantiate our observation we further
studied patterns of distribution of these variations across
24 Indian populations residing at different geographical
locations. We observed that populations that reside in
lower altitude but are genetically similar to the natives
have a significantly lower frequency of the Pitta
genotypes. In addition, we also observed the marker linked
to high altitude adaptation in India to be conserved across
different world populations residing at high altitude
13
. Thus
we anticipate that individuals who are of the Pitta Prakriti
or who have the marker linked to the high altitude
phenotype may be able to perform better in high altitude
conditions. Thus using the Ayurgenomics approach we
could identify pathways and genes that differ at the
expression level as well as genetic level between
contrasting constitution types that are differently
predisposed. Led by this observation we subsequently
discovered a genetic marker in an oxygen sensing gene
that confers differences in responsiveness to low oxygen
(hypoxia) and was found to be responsible for high altitude
adaptation
13
. A conventional approach wherein inherent
molecular differences amongst healthy individuals.
Our studies have provided a molecular framework for
Ayurgenomics and further studies need to be undertaken
to understand the holistic concepts of this system of
medicine. These studies have highlighted that an
Ayurgenomics approach can accelerate/assist predictive
marker discovery. World-over, different approaches are now
being taken to find solutions for addressing the issue of
“missing heritability” – the dark hole in the genetic studies.
This has brought in a new era of system biology for
holistic understanding of diseases and integrative
approaches involving more omics (proteomics,
transcriptomics, metabolomics) and intensive economics’
are being adapted. In this context, validation of the tenets
of Ayurveda and subsequent integration of Ayurveda
phenotyping in complex diseases has the potential to be
the least invasive and most affordable form of assessing
an individual’s susceptibility and prognosis. Further it
could guide therapeutic and dietary recommendations.
Presently we are trying to develop objective measures of
the phenotyping concepts that would allow global
standards to be set for different constitution types. So far
Ayurveda has been principally been explored to identify
active principles from herbs described in the treatment of
different disease although a rigorous testing of the tenet
on which these medicinal plants are described to be
effective has not been attempted. Our efforts are towards
establishing the molecular basis of the principles of
Ayurveda in order to expand the scope of applicability
and global acceptability of this branch of science.
Acknowledgements
We thank Prof. Samir K. Brahmachari for conception
of Ayurgenomics and also the Indian Genome Variation
project. Financial support from the Department of Science
and Technology (DST) Grant B6.25 (to M.M.) to help
initiate the project, and Council of Scientific and Industrial
Research Grants CMM0016 and MLP3601 (to M.M.) is also
acknowledged. S
References
1. JC Venter et al The sequence of the human genome.
Science; 291(5507):1304-51 (2001).
2. E Lander et al Initial sequencing and analysis of the human
genome.Nature; 409 (6822):860-921 (2001).
3. The International HapMap Consortium. The International
HapMap Project. Nature 18; 426 (6968):789-96 (2003).
VOL. 77, NOS. 1–2 17
4. The International HapMap Consortium. A second generation
human haplotype map of over 3.1 million SNPs Nature 449,
851-861 (2007).
5. LA Hindorff, P Sethupathy, HA Junkins, E M Ramos, J P
Mehta, FS Collins and TA Manolio . Potential etiologic and
functional implications of genome-wide association loci for
human diseases and traits Proc. Natl. Acad. Sci. USA 106:
9362-9367 (2009).
6. KA Frazer, SS Murray, NJ Schork, EJ Topol. Human genetic
variation and its contribution to complex traits Nat. Rev.
Genet. 10: 241-251 (2009).
7. Caraka Samhita (Text with English translation).
Chaukhamba Orientalia; (2000).
8. Susruta Samhita (Text with English translation).
Chaukhamba Visvabharati; (2000).
9. MS Valiathan: The Legacy of Caraka. Orient Longman;
(2003).
10. PV. Sharma Caraka Samhita (Text with English translation)
(Chaukhamba Orientalia, Varanasi, India) (2000).
11. P Bhushan, J Kalpana and C Arvind Classification of human
population based on HLA gene polymorphism and the
concept of Prakriti in Ayurveda. J. Altern. Complement
Med, 11: 349-353 (2005).
12. B Prasher, S Negi, S Aggarwal, AK Mandal, TP Sethi, SR
Deshmukh, SG Purohit, S Sengupta, S Khanna, F
Mohammad, G Garg, SK Brahmachari, Indian Genome
Variation Consortium, Mukerji M Whole genome expression
and biochemical correlates of extreme constitutional types
defined in Ayurveda. J. Transl. Med. 6:48. :48 (2008)
13. S Aggarwal, S Negi, P Jha, PK Singh, T Stobdan, MA
Pasha, S Ghosh, A Agrawal, Indian Genome Variation
Consortium, Prasher B, Mukerji M EGLN1 involvement in
high altitude adaptation revealed through genetic analysis
of extreme constitution types defined in Ayurveda Proc.
Natl. Acad. Sci. U S A. 2010 Oct 18. (2010) [Epub ahead
of print]
Website references
z The Human Genome Project (http://www.ornl.gov/sci/
techresources/Human_Genome )
z The International HapMap Project http://
hapmap.ncbi.nlm.nih.gov/
z A Catalog of Published Genome-Wide Association Studies.
http:// www.genome.gov/gwastudies
... Body constitution is used to classify the body type of an individual, which allows for the provision of individualized guidance for health promotion, disease prevention and treatment in the population [21,22]. It is a common practice to use scales to measure and identify body constitution in traditional medicine [23][24][25]. ...
Article
Abstract Background: The constitutional theory is an important aspect of Tibetan medicine, however a quantitative measurement tool for constitution identification still does not exist. The objective of this study is to evaluate the reliability and validity of a Tibetan medicine constitution scale (TMCS) that consists of three sub-scales and 31 items. Methods: From June to July 2019, 622 people from the general population in Beijing, China, aged 18 to 60 were investigated. We employed Cronbach’s alpha (α), split-half reliability, and test-retest reliability to determine the reliability of the scale. The content validity and contract validity of the TMCS were evaluated using factor analysis and correlation analysis based on Tibetan medicine theory. The items were screened according to the reliability test results. Results: After the items were screened, 22 items remained in the scale. The Cronbach’s alpha value for the internal consistency reliability of the TMCS was 0.754 (95% confidence interval (CI): 0.700-0.761). The correlation coefficient for the two-week test-retest of the total score was 0.726 (95% CI: 0.571-0.834). The split-half coefficient was 0.689 (95% CI: 0.640-0.734). The scale can be explained by eight potential factors, including morphological structure, physiological function, personality, adaptability, etc. The body mass index was negatively correlated with the score of the sub-rlung scale (r = - 0.376), slightly positively correlated with the sub-mkhris pa scale (r = 0.099), and positively correlated with the sub-bad kan scale (r = 0.362). Conclusion: The TMCS is a reliable and valid instrument that can be used to assess the body constitution of the general population in Beijing, China. Future studies are needed to explore the differences in biological characteristics among the constitutional types and the association between constitution and disease.
... Body constitution is used to classify the body type of an individual, which allows for the provision of individualized guidance for health promotion, disease prevention and treatment in the population [21,22]. It is a common practice to use scales to measure and identify body constitution in traditional medicine [23][24][25]. ...
Article
Full-text available
Background: The constitutional theory is an important aspect of Tibetan medicine, however a quantitative measurement tool for constitution identification still does not exist. The objective of this study is to evaluate the reliability and validity of a Tibetan medicine constitution scale (TMCS) that consists of three sub-scales and 31 items. Methods: From June to July 2019, 622 people from the general population in Beijing, China, aged 18 to 60 were investigated. We employed Cronbach’s alpha (α), split-half reliability, and test-retest reliability to determine the reliability of the scale. The content validity and contract validity of the TMCS were evaluated using factor analysis and correlation analysis based on Tibetan medicine theory. The items were screened according to the reliability test results. Results: After the items were screened, 22 items remained in the scale. The Cronbach’s alpha value for the internal consistency reliability of the TMCS was 0.754 (95% confidence interval (CI): 0.700-0.761). The correlation coefficient for the two-week test-retest of the total score was 0.726 (95% CI: 0.571-0.834). The split-half coefficient was 0.689 (95% CI: 0.640-0.734). The scale can be explained by eight potential factors, including morphological structure, physiological function, personality, adaptability, etc. The body mass index was negatively correlated with the score of the sub-rlung scale (r = - 0.376), slightly positively correlated with the sub-mkhris pa scale (r = 0.099), and positively correlated with the sub-bad kan scale (r = 0.362). Conclusion: The TMCS is a reliable and valid instrument that can be used to assess the body constitution of the general population in Beijing, China. Future studies are needed to explore the differences in biological characteristics among the constitutional types and the association between constitution and disease.
... In 2008 and 2010, papers began promoting the idea of the connection between Ayurveda and genomics [23,24]. In 2011, a review and theoretical papers appeared in which the term Ayurgenomics was presented [25][26][27][28]. Since 2012, there have been many theoretical and review papers on Ayurgenomics from different angles [29][30][31][32][33][34][35][36][37][38][39][40][41]. ...
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Within the disciplines of modern medicine, P4 medicine is emerging as a new field which focuses on the whole patient. The development of Ayurgenomics could greatly enrich P4 medicine by providing a clear theoretical understanding of the whole patient and a practical application of ancient and modern preventative and therapeutic practices to improve mental and physical health. One of the most difficult challenges today is understanding the ancient concepts of Ayurveda in terms of modern science. To date, a number of researchers have attempted this task, of which one of the most successful outcomes is the creation of the new field of Ayurgenomics. Ayurgenomics integrates concepts in Ayurveda, such as Prakriti, with modern genetics research. It correlates the combination of three doshas, Vata, Pitta and Kapha, with the expression of specific genes and physiological characteristics. It also helps to interpret Ayurveda as an ancient science of epigenetics which assesses the current state of the doshas, and uses specific personalized diet and lifestyle recommendations to improve a patient’s health. This review provides a current update of this emerging field.
... In one study maximum cases of Vata Prakriti (71%) have less than 20 BMI followed by Pitta Prakriti, (19%) and Kapha (10%) Prakriti respectively. The moderate BMI (20)(21)(22)(23)(24)(25) was found more in Kapha Prakriti individuals (47%) followed by Vata Prakriti (32%) and Pitta Prakriti (21%), respectively. BMI more than 25 were mainly found in Kapha Prakriti individuals (79%) followed by Vata Prakriti, (11%) and Pitta Prakriti, (44%) respectively 36 . ...
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Background: Ayurveda is an ancient system of personalized medicine, documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as the therapy and lifestyle regime. Ayurveda describes seven broad Prakriti (Physical constitution) Prakriti is defined as the sum of physical, physiological, psychological traits of an individual which represents genotypes. Objective: In this article we have attempted to narrate concepts of Prakriti and its relation with hematological parameter, body mass index, blood groups and genotypes. Material and Method: Present article is based on critical review of Ayurvedic textual information, published research works, modern literature and research works conducted at various institutes. The possible correlation has been made between collected information and has been presented in systematic way. Result: In Pitta Prakriti individual's hematological parameters like Hemoglobin (Hb%), Packed cell volume (PCV), and Red blood corpuscles (RBC) count are significantly on the higher side of normal range in comparison to Vata and Kapha Prakriti. Higher level of cluster of differentiation (CD) 14 markers in Pitta Prakriti, CD25 and CD56 in Kapha Prakriti individuals. Vata Prakriti individuals have "A" blood group, maximum Pitta Prakriti individuals have "O" blood group while maximum Kapha Prakriti individuals have "B" blood group and genotype correlation shows that HLA DRB1 ((human leukocyte antigen, dimer beta chain) gene polymorphism, CYP2C19 (Cytochrome P450 2C19) gene polymorphism and PGM1 (Phosphoglucomutase 1) polymorphism have scientific variations with the human Prakriti concept. Conclusion: Prakriti of individual has strong relation with Hematological parameters (CBC, lipid profile, Liver function test (LFT)), Body mass index (BMI), anthropometry, blood groups and genotypes.
... Developing a strategy to address this concern and obtain homogeneous sample sets may be the most rewarding. One such emerging strategy is 'Ayurgenomics'-that is a combination of deep phenotyping principles practised in Ayurveda (the Indian traditional system of medicine) and contemporary genome analysis tools (Thelma 2008;Mukerji and Bhavana 2011;Juyal et al. 2012;Govindaraj et al. 2015;Prasher et al. 2016), which may fulfil this need. In this approach, every individual is categorized into one of the specific constitution (prakriti) groups of vata, pitta and kapha predominant or mixed prakriti using the Ayurveda criteria. ...
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Neurodegenerative diseases constitute a large proportion of disorders in elderly, majority being sporadic in occurrence with ∼5-10% familial. A strong genetic component underlies the Mendelian forms but nongenetic factors together with genetic vulnerability contributes to the complex sporadic forms. Several gene discoveries in the familial forms have provided novel insights into the pathogenesis of neurodegeneration with implications for treatment. Conversely, findings from genetic dissection of the sporadic forms, despite large genomewide association studies and more recently whole exome and whole genome sequencing, have been limited. This review provides a concise account of the genetics that we know, the pathways that they implicate, the challenges that are faced and the prospects that are envisaged for the sporadic, complex forms of neurodegenerative diseases, taking four most common conditions, namely Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington disease as examples. Poor replication across studies, inability to establish genotype-phenotype correlations and the overall failure to predict risk and/or prevent disease in this group poses a continuing challenge. Among others, clinical heterogeneity emerges as the most important impediment warranting newer approaches. Advanced computational and system biology tools to analyse the big data are being generated and the alternate strategy such as subgrouping of case-control cohorts based on deep phenotyping using the principles of Ayurveda to overcome current limitation of phenotype heterogeneity seem to hold promise. However, at this point, with advances in discovery genomics and functional analysis of putative determinants with translation potential for the complex forms being minimal, stem cell therapies are being attempted as potential interventions. In this context, the possibility to generate patient derived induced pluripotent stem cells, mutant/gene/genome correction through CRISPR/Cas9 technology and repopulating the specific brain regions with corrected neurons, which may fulfil the dream of personalized medicine have been mentioned briefly. Understanding disease pathways/biology using this technology, with implications for development of novel therapeutics are optimistic expectations in the near future.
... This study was suggestive of increased levels of markers of metabolic syndrome combined with over expression of genes involved in inflammatory response in individuals with kapha predominance. [20,21] The study has similar results suggestive of kapha prakriti individuals having higher body fat with higher BFMI. Ayurveda describes sedentary lifestyle contributes to vitiation of kapha, meda (fat) and mutra (urine); that in turn is responsible for the commencement of Madhumeha or Diabetes. ...
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Background: There has been keen research interest in exploring Indian Traditional Medicine of Ayurveda which comprises thousands of medical concepts and hypothesis. Due to increase in scientific validation in various concepts, Ayurveda has got its deserved recognition and its scientific endeavor has increased significantly in the past decade. Aims and Objectives: The aim of this study is to compare different anthropometric indices along with body composition analysis parameters in individuals with dominant primary dosha of Ayurvedic Tridosha Concept. Materials and Methods: A cohort study was designed and conducted from January 2016 to December 2016. Healthy participants aged between 18 and 22 years willing to participate in the study were included in the study. Questionnaires were administered to collect information including demographic data, certain physical and psychological characteristics to assess the Ayurvedic Prakriti of the individual. The individuals were examined by an Ayurvedic Physician for assessment of Prakriti by physical examination. Anthropometric parameters such as waist circumference, height, weight, body mass index (BMI) and hip circumference were measured. Total body composition was assessed using Bodystat1500MD. Results: The participants with the dominance of kapha prakriti had significantly higher BMI, fat mass index and basal metabolic rate compared to vata and pitta groups. Conclusions: This study highlights the use of an assessment of Prakriti as a screening tool for obesity.
... This study was suggestive of increased levels of markers of metabolic syndrome combined with over expression of genes involved in inflammatory response in individuals with kapha predominance. [20,21] The study has similar results suggestive of kapha prakriti individuals having higher body fat with higher BFMI. Ayurveda describes sedentary lifestyle contributes to vitiation of kapha, meda (fat) and mutra (urine); that in turn is responsible for the commencement of Madhumeha or Diabetes. ...
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