ROLE OF VITAMIN D RECEPTOR (VDR) GENE POLYMORPHISM

Abstract

Vitamin D deficiency leads to poor bone development and general
health.
Newly converted calcitriol binds to the VDR protein, as encoded for by the VDR gene. VDR is expressed in most tissues of the body and there are several forms of VDR genes depicting polymorphism. There are four most common polymorphic forms found within the VDR gene are and these are referred as rs2228570, rs1544410, rs7975232 and
rs731236. These are also known traditionally as FokI, BsmI, ApaI and TaqI, respectively.
esults of the various studies discussed here will broaden our understanding of variability in the Vitamin D and might help us in assessing

The main source of vitamin D is dermal and amount synthesized depends upon exposure to sunlight. Additional amounts can also be obtained from food or through dietary supplementation. The inactive form of vitamin D is converted to its active form called calcitrol in liver and kidney, which is further utilized by variety of tissues, and its action is mediated via the vitamin D receptor (VDR).
The role of polymorphic forms has been explored in recent years with genes linked to cardiovascular, autoimmune, humoral, pulmonary and neurological diseases. Inadequate levels of vitamin D in the body were found to be associated with various disorders such as Alzheimer, diabetes, heart disease, cancers etc. VDR gene polymorphism also found to influence the allograft outcomes in recipients of renal transplants. The goal of this review is to highlight the role of VDR gene polymorphism in especially in altering Bone Mass Density (BMD), degenerative disc disease, osteoporosis, rickets and other conditions such as breast cancer, allograft survival in renal transplant recipients, new onset diabetes at transplant,
hepatitis B infection and chronic periodontitis.

Full text

www.wjpps.com Vol 6, Issue 7, 2017.
1083
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
ROLE OF VITAMIN D RECEPTOR (VDR) GENE POLYMORPHISM
Balwant Chauhan1*and Prashant Sakharkar2
1Department of Biopharmaceutical Sciences, Roosevelt University College of Pharmacy,
Schaumburg, IL 60173 USA.
2Department of Clinical and Administrative Sciences, Roosevelt University College of
Pharmacy, Schaumburg, IL 60173 USA.
ABSTRACT
Vitamin D deficiency leads to poor bone development and general
health. The main source of vitamin D is dermal and amount
synthesized depends upon exposure to sunlight. Additional amounts
can also be obtained from food or through dietary supplementation.
The inactive form of vitamin D is converted to its active form called
calcitrol in liver and kidney, which is further utilized by variety of
tissues, and its action is mediated via the vitamin D receptor (VDR).
Newly converted calcitriol binds to the VDR protein, as encoded for by
the VDR gene. VDR is expressed in most tissues of the body and there
are several forms of VDR genes depicting polymorphism. There are
four most common polymorphic forms found within the VDR gene are
and these are referred as rs2228570, rs1544410, rs7975232 and
rs731236. These are also known traditionally as FokI, BsmI, ApaI and TaqI, respectively. The
role of polymorphic forms has been explored in recent years with genes linked to
cardiovascular, autoimmune, humoral, pulmonary and neurological diseases. Inadequate
levels of vitamin D in the body were found to be associated with various disorders such as
Alzheimer, diabetes, heart disease, cancers etc. VDR gene polymorphism also found to
influence the allograft outcomes in recipients of renal transplants. The goal of this review is
to highlight the role of VDR gene polymorphism in especially in altering Bone Mass Density
(BMD), degenerative disc disease, osteoporosis, rickets and other conditions such as breast
cancer, allograft survival in renal transplant recipients, new onset diabetes at transplant,
hepatitis B infection and chronic periodontitis. Results of the various studies discussed here
will broaden our understanding of variability in the Vitamin D and might help us in assessing
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
S SJIF Impact Factor 6.647
Volume 6, Issue 7, 1083-1095 Research Article ISSN 2278 – 4357
*Corresponding Author
Balwant Chauhan
Department of
Biopharmaceutical Sciences,
Roosevelt University
College of Pharmacy,
Schaumburg, IL 60173
USA.
Article Received on
01 May 2017,
Revised on 20 May 2017,
Accepted on 10 June 2017
DOI: 10.20959/wjpps20177-9500

www.wjpps.com Vol 6, Issue 7, 2017.
1084
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
risk of the disease as a predictive marker and in predicting the treatment response.
KEYWORDS: Vitamin D; vitamin D receptor; VDR gene; polymorphism; VDR gene
polymorphism; allograft outcomes.
INTRODUCTION
Vitamin D refers to a group of fat-soluble secosteroids and is important for intestinal
absorption of calcium, phosphate, magnesium and zinc. It is well known that the vitamin D
deficiency leads to poor bone development and health. Vitamin D maintains healthy calcium
and phosphate levels by aiding the absorption of calcium from the intestine in the body as
well as by influencing kidney function.[1] Calcium homeostasis maintained by vitamin D
improves the strength of human bones by increasing bone density and thereby preventing
bone disease such as osteoporosis and rickets.
Skin is the main source of vitamin D. Amount of Vitamin D synthesized depends upon skin’s
exposure to sunlight. Most important vitamin D forms are: vitamin D2 (ergocalciferol) and
vitamin D3 (cholecalciferol). Both forms are ingested from the diet and supplements. These
forms are biologically inactive and require enzymatic conversion in the liver and kidney.
Vitamin D is converted in the liver to calcifediol (=prohormone) and ergocalciferol (vitamin-
D2). Vitamin D2 is converted to 25-hydroxyergocalciferol [25-hydroxyvitamin D2-
abbreviated as 25(OH)2 D2]. Some of the calcifediol which has entered in kidney is converted
to calcitriol (1, 25-dihydroxycholecalciferol, abbreviated as 1, 25 (OH)2 D3 (=hormone), is
biologically activated form.[2] Calcitriol plays major role in calcium and phosphate
homeostasis and also affects immune and neuromuscular functions. Calcitriol is released into
the blood circulation. It binds to vitamin D-binding protein (VDBP), which is a career protein
in plasma and is transported to various tissues/organs. In addition to skin, liver and kidney,
calcitriol is also synthesized by immune system cells like monocyte /macrophages. Calcitriol
is a potent ligand of vitamin D receptor (VDR). Hormone binds to VDR in the nucleus. How
signal transduction progresses in nucleus and how cellular functions are altered is depicted in
Figure 1. VDR belongs to the nuclear receptor superfamily of steroid/thyroid hormone
receptors. VDRs are expressed in most of the organs including skin, breast, brain, gonads,
heart, parathyroid glands and prostate. Figure 2 summarizes the role possibly played by
hormone-VDR complex. Mutations in VDR can affect the regulation of expression of various
genes; therefore, VDR gene polymorphism is very important to understand the role played by
vitamin-D3 and VDR complex. There are four most common polymorphic forms found

www.wjpps.com Vol 6, Issue 7, 2017.
1085
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
within the VDR gene. These are referred as rs2228570, rs1544410, rs7975232 and rs731236.
These are also traditionally known as FokI, BsmI, ApaI and TaqI, respectively.[3]
The BsmI, ApaI and TaqI polymorphisms are strongly associated with one another and the
presence of one polymorphism can predict the presence of the others, as they almost always
occur together. In this regard they are haplotypes and are tagged. This is a good example of
what is known as linkage disequilibrium.
The role of vitamin D has been explored in recent years with functions affecting 229 human
genes linked to cardiovascular, autoimmune, humoral, pulmonary and neurological
diseases.[4] Inadequate levels of vitamin D in the body were found associated with various
disorders such as Alzheimer, diabetes, heart disease, cancers etc.[5-8] VDR gene
polymorphism also influences the allograft outcomes in recipients of renal transplants.[9]
Tumor growth of the epithelial cells of the skin, breast, prostate and colon as well as
inflammation are regulated by vitamin D through number of signaling pathways. Some of the
outcomes (high plasma levels of vitamin D resulting in hypercalcemia) are attributed to the
cytokine interferon gamma (IFN-γ), and through macrophage immune function activation,
which has been associated with the negative impact on graft outcomes in renal transplant
patients.[10] IFN-γ polymorphisms on the other hand have been associated with BK virus
nephropathy and cytomegalovirus infection.[11-12] The goal of this review is to highlight the
role of VDR gene polymorphism especially in BMD, degenerative disc disease, osteoporosis,
rickets and other conditions such as breast cancer, allograft survival in renal transplant
recipients, new onset diabetes at transplant, hepatitis B infection and chronic periodontitis.
Role and Impact of VDR Gene Polymorphism
Potential association of VDR gene polymorphisms ApaI, BsmI, FokI and TaqI with bone
mineral density (BMD) was examined by Mitra and colleagues in 246 postmenopausal Indian
women in one study. Osteoporosis is very common in postmenopausal women. BMD, which
is a major determinant of osteoporotic fracture risk, has a particular genetic background. This
study revealed that VDR gene polymorphisms are associated with BMD in Indian women.
The average BMD at spine and hip of women with genotypes aa, bb (presence of restriction
sites for ApaI and BsmI), FF and TT (absence of restriction sites for FokI and TaqI) was
found more than 10% higher than those with genotypes AA, BB, ff and tt, respectively. Also,
the combinations between BsmI, ApaI and TaqI genotypes showed significant effect on BsmI-
ApaI genotypes combination on BMD.[13]

www.wjpps.com Vol 6, Issue 7, 2017.
1086
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
To study the association of VDR gene polymorphisms with bone tissue mineral density and
biochemical marker of 25-PO vitamin D in adolescents of both ethnic groups (Aktobe-
Kazakh group and Slavonic- Russian group), living in Western Kazakhstan Region, 110
relatively healthy children aged 13-18 years of Aktobe, the representatives of Kazakh ethnic
group, 66 (Kazakh children) and Slavonic e 44 (Russian children) were included in this
study.[14]
Genotype SS was found to be a negative marker in Kazakh adolescents of Western
Kazakhstan Region for bone tissue mineral density (BTMD) and 25-PO vitamin D; whereas,
in children of Kazakh nationality with osteopathy sign, genotype SS occurred at almost twice
the rate in comparison with Slavonic ethnic group and respectively by a factor of 2 less 25-
PO vitamin D content, suggesting that disorders of bone mineralization and metabolism
depend on ethnic affiliation and presence of defined polymorphic genotypes of VDR gene
molecular markers.[14]
In another study, the VDR gene polymorphism in a healthy adult Brazilian population was
determined in a group of patients with insulin dependent diabetes mellitus (IDDM) and
correlated with the findings with densitometric values in both groups. The VDR genotype
was assessed by polymerase chain reaction amplification followed by BsmI digestion on
DNA isolated from peripheral blood leukocytes. The IDDM group had a lower BMD
compared with the control group. The VDR genotype distribution did not differ from that
observed in the IDDM group. In the IDDM group, patients with the Bb genotype had a higher
body weight when compared with the BB genotype. However, when age, sex and body mass
index was controlled in diabetic patients on regression analysis, BB genotype was associated
with a lower mean BMD at lumbar spine and femoral neck than in Bb and bb patients. BB
patients had a shorter duration of IDDM than bb and Bb patients. These findings suggested a
small influence of VDR gene polymorphism on BMD of a racially heterogeneous population
with IDDM.[15]
To evaluate the contribution of VDR gene polymorphism in the ethnic groups for bone mass
in mother and children of different ethnic origins, the VDR genotypes and bone mass in 43
African-American and white women and their children were studied. All children had a
whole body bone mass measurement at age 9. Thirty nine children had follow up
measurements at age 11, while all the mothers had a single measurement. Significant ethnic
difference in the VDR genotype frequencies among the adults and the children were

www.wjpps.com Vol 6, Issue 7, 2017.
1087
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
observed. No African-American subjects had the genotype “BB”, whereas, there was a 25%
frequency of the “BB” genotype in the white adults and 24% in the white children. After
pooling the ethnic groups, the mean bone mass in the “bb” genotype was found significantly
higher than in the “BB” genotype among the mothers, but this was not found in the children
at baseline. However, by age 11, those with the “Bb” or “bb” genotypes had a larger gain in
bone mass than those with “BB”. These findings supported the suggestion that the ethnic
difference in VDR genotype frequencies may help to explain the well known ethnic
differences in bone mass and genotypes. Further, these observations suggested that VDR
polymorphism may have an effect on bone mass during puberty as peak bone mass is
accumulated during this phase of life.[16]
Allelic frequencies of the BsmI, ApaI, and TaqI were measured using restriction fragment
length polymorphisms (RFLPs) in 144 normal healthy southern Chinese premenopausal
women aged between 30 and 40 years and correlation to their peak bone mass with the VDR
genotypes was studied in one study. The B allele of the BsmI restriction-site was found only
in 5% of the Chinese population compared to western populations. The BBAAtt genotype
was found virtually nonexistent in Chinese people. Analysis of the VDR genotype revealed
that subjects with BbAaTt and BbAATt haplotypes had the lowest peak bone mass. Although
VDR polymorphism is believed to affect calcium absorption, this study failed to confirm a
strong relationship between the VDR genotype and peak bone mass in Southern Chinese
population with low dietary calcium intake. [17]
The effect of the TaqI alleles in vitamin D receptor was assessed on the risk of developing
degenerative disc disease in a Southern Chinese population. Lumbar degenerative disc
disease was defined by magnetic resonance imaging (MRI) in 804 Southern Chinese
volunteers between 18 and 55 years of age. The t allele of TaqI in VDR gene was
significantly associated with degenerative disc disease. Further subgroup analysis showed
that in individuals younger than 40 years, the likelihood of degenerative disc disease was five
times higher. Similarly, disc bulge was significantly associated with t allele in individuals
younger than 40 years. This was the largest scale genetics study to date using MRI to define
precisely degenerative disc disease in the Southern Chinese population, which has showed
that the t allele of vitamin D receptor TaqI is associated with a high risk of degenerative disc
disease and disc bulge developing, especially in individuals younger than 40 years. [18]

www.wjpps.com Vol 6, Issue 7, 2017.
1088
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
Restriction pattern of the polymerase chain reaction product of the VDR gene with the Bsm1
enzyme and serum osteocalcin in patients with osteoporosis was examined to evaluate if
common allelic variants in the gene encoding the VDR are useful in predicting differences in
bone mineral density (BMD) and bone turnover rate in Koreans. The prevalence of the BB
genotype in the controls was extremely low when compared with that in other reports. Only
2.8% of those patients with osteoporosis had the BB genotype. In contrast, 12.5% had the Bb
genotype, and 84.7% had the bb genotype. The prevalence of the BB genotype in patients
with severe osteoporosis was found to be extremely low: the BB, Bb, and bb genotypes
accounted for 0%, 12.4%, and 87.6%, respectively. Compared with the mean serum
osteocalcin level of the pre and post menopausal controls, the level in patients with severe
osteoporosis was significantly higher. These results suggested that restriction fragment length
polymorphism analysis of the VDR gene with a Bsm1 restriction enzyme in Koreans is not
helpful for early detection of patients at risk of developing osteoporosis. [19]
In another study conducted in Nigeria, VDR polymorphisms and susceptibility of some
children to develop rickets in the setting of low calcium intake were compared. VDR
genotypes were determined by the presence or absence of Bsm I, Apa I, Taq I, and Fok I
restriction enzyme cleavage sites. This study involved 105 children with active nutritional
rickets and 94 subjects’ representative of the community from which the children with
Rickets came from. The ff genotype was less common in the rickets group compared to the
community group. Findings of this study raised the possibility that VDR alleles might be
important in determining an individual's susceptibility to developing rickets when faced with
dietary calcium deficiency.[20]
A study was performed to determine the influence of VDR gene polymorphism on breast
cancer risk in Taiwan, which has a low incidence of breast cancer. Polymorphisms in the
VDR gene were genotyped for 34 Taiwanese women with sporadic breast cancer, 46 with
benign breast tumors and 169 cancer-free female (cohort controls). The ApaI, TaqI, and BsmI
polymorphisms in the 3′ end of the VDR gene were associated with breast cancer risk, with a
trend for increasing risk with increased numbers of BsmI B> B alleles and ApaI >AA
genotypes. These findings indicated that the AA genotype may be associated with an
increased risk of breast cancer, while the Aa genotype tends to be associated with decreased
risk. These results suggest that polymorphic variation in or near the 3′ end of the VDR gene
may influence breast cancer risk in Taiwanese women and justifies further investigation of

www.wjpps.com Vol 6, Issue 7, 2017.
1089
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
the role of VDR polymorphism for sporadic breast cancer in low-incidence areas. These
findings may help when designing the targeted therapy in future.[21]
In a study by Vu and colleagues, polymorphisms of VDR genes and Vitamin D binding
protein (VDBP) were studied for their association with allograft survival or acute rejection in
renal transplant recipients of Hispanic ethnicity.[9] A total of 502 Hispanic renal allograft
recipients were genotyped for four different single nucleotide polymorphisms (SNPs) of
VDR. Findings of this study indicated that VDBP (rs4588) and VDR gene polymorphisms
(rs1544410) are associated with allograft survival or rejection. These findings provided an
important insight about Vitamin D polymorphism that affects allograft survival. Identifying
this gene polymorphism in patients may prove useful in clinical practice as a predictive
marker for triage patients who may have greater success with their allograft survival. [9]
The VDR gene polymorphisms in 379 renal transplant recipients were genotyped for VDR
(FokI & ApaI) and the association of each genotype with renal allograft survival and acute
rejection were determined in a study by Lavin and colleagues.[22] Significant improved
allograft survival was observed for patients who were homozygous or heterozygous for the
VDR FokI T allele further suggesting that the chronic allograft rejection can be prevented
with the use of right Vitamin D receptor agonists. [22]
VDR gene polymorphism, Taq1 A/G located in exon 9 and its association with the
development of new onset diabetes at transplant (NODAT) in Hispanic renal transplant
recipients (RTRs) was examined. NODAT is an important metabolic complication that
increases risk of cardiovascular disease and is associated with lower allograft and patient
survival in RTRs. A total of 129 RTRs with no evidence of pre-existing diabetes who
developed NODAT and 186 controls with no history of diabetes were included in this study.
The Taq1 A/G (rs731236) polymorphism was genotyped using polymerase chain reaction-
restriction fragment length polymorphism analysis. The genotype frequency of the Taq1 A/G
polymorphism differed significantly between NODAT patients and controls. Kaplan-Meier
survival analysis also suggested more than 1.9 fold increased risk of allograft failure in
NODAT patients. After 3 years, graft survival began to decrease in the NODAT group
compared with control group. Findings of this study indicated that the Taq1 polymorphism of
VDR is significantly associated with NODAT. [23]

www.wjpps.com Vol 6, Issue 7, 2017.
1090
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
A possible association between the VDR, SNPs, and hepatocellular carcinoma (HCC) in
patients with chronic hepatitis B virus (HBV) infection was explored in this study. A total of
968 chronic HBV infection patients were enrolled, of which 436 patients were diagnosed
HCC patients, and 532 were non-HCC patients. The clinical and pathological characteristics
of HCC and the genotypes of VDR gene at FokI, BsmI, ApaI, and TaqI were determined. The
genotype frequencies of VDR FokI C>T polymorphism differed significantly between HCC
and non-HCC groups. HCC patients had a higher prevalence of FokI TT genotype than non-
HCC subjects. With FokI CC as reference, the TT carriage had a significantly higher risk for
development of HCC after adjustments with age, sex, HBV infection time, α-fetoprotein,
smoking status, and alcohol intake. In addition, the TT genotype carriage of FokI
polymorphisms were associated with advanced tumor stage, presence of cirrhosis, and lymph
node metastasis. The SNP at BsmI, ApaI, and TaqI did not show any positive association with
the risk and clinical and pathological features of HCC. Findings of this study suggested that
the FokI C>T polymorphisms may be used as a molecular marker to predict the risk and to
evaluate the disease severity of HCC in those infected with HBV. [24]
In another study, association of polymorphisms in VDR gene exons with the incidence of
Chronic Periodontitis (CP) was examined. CP is caused by enhanced resorption of the
alveolar bone supporting the teeth and is associated with intraoral inflammation after
infection with certain bacteria. The VDR gene polymorphism was reported recently to be
significantly related to the occurrence of tuberculosis and infection of chronic hepatitis B
virus. This may be interpreted to indicate a close relationship between VDR gene
polymorphism and the immunological action, because vitamin D activates monocytes,
stimulates cell-mediated immunity, and suppresses lymphocyte proliferation. [25]
This was a case-controlled study with a group of 168 unrelated Japanese subjects whose ages
ranged from 35 to 65 years. The Taq I polymorphism in the VDR gene was found to be
associated significantly with CP. The TT genotype was found to be associated with CP, and
with well-recognized risk factors, smoking and diabetes on multiple logistic regression
analyses. This indicated that the VDR gene polymorphism (TT genotype) is a risk factor for
CP, independent of smoking and diabetes. [25]

www.wjpps.com Vol 6, Issue 7, 2017.
1091
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
Table 1: VDR gene polymorphism and its impact on disease conditions.
Polymorphism
SNP
Disease Conditions
FokI
rs2228570
Breast cancer, allograft survival in renal transplant,
hepatocellular carcinoma
Apa I
rs 7975232
BMD, breast cancer
Taq I
rs 731236
BMD, degenerative disc diseases, breast cancer, new
onset diabetes at transplant, chronic periodontitis
Bsm I
rs 1544410
BMD, breast cancer, allograft survival in renal
transplant
SNP- Single nucleotide protein; BMD- Bone mineral density.
Figure 1: Vitamin D Synthesis, Activation and Cellular Response.
(Adapted and modified from: Haussler et al. The Vitamin D hormone and its nuclear
receptor: molecular actions and disease states. Journal of Endocrinology. 1997; 154:557-573)

www.wjpps.com Vol 6, Issue 7, 2017.
1092
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
Figure 2: Role of vitamin D and vitamin D receptor (VDR).
CONCLUSIONS
Polymorphisms in the VDR gene have been linked to several diseases (Table 1). Recent
studies have indicated that many polymorphisms exist in the VDR gene, however their
influence on VDR protein function are largely unidentified. Research is therefore focused on
documenting additional polymorphisms across the VDR gene and trying to understand the
functional consequences of such variations. Eventually, results of these research studies will
broaden our understanding of variability in the Vitamin D receptor (VDR) gene and might
help us in assessing risk for the disease as a predictive marker and in predicting the treatment
response.
REFERENCES
1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium
and Vitamin D. Washington, DC: National Academy Press, 2010.
2. Jurutka PW, Whitfield GK, Hsieh JC, Thompson PD, Haussler CA, Haussler MR.
Molecular nature of the vitamin D receptor and its role in regulation of gene
expression. Rev Endocr Metab Disord, 2001; 2(2): 203–16.

www.wjpps.com Vol 6, Issue 7, 2017.
1093
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
3. Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA. Vitamin D receptor
gene polymorphisms in relation to Vitamin D related disease states. J Steroid Biochem
Mol Biol, 2004; 89-90(1–5): 187–93. pmid:15225770. Epub 2004/07/01. eng.
4. Lucky MH,Baig S. The Vitamin D Receptor (VDR) Gene Polymorphisms Fok1 In Obese
Pakistanis– a Preliminary Report. Int J Adv Biol Biom Res, 2015; 3(3): 257-262 .
5. Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in
Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis, 2013;
33(3): 659-74.
6. Huang Y, Li X, Wang M, et al. Lipoprotein lipase links vitamin D, insulin resistance, and
type 2 diabetes: a cross-sectional epidemiological study. Cardiovasc Diabetol, 2013; 12:
17.
7. Karakas M, Thorand B, Zierer A, et al. Low levels of serum 25-hydroxyvitamin D are
associated with increased risk of myocardial infarction, especially in women: results from
the MONICA/KORA Augsburg case-cohort study. J Clin Endocrinol Metab, 2013; 98(1):
272-80.
8. Krishnan AV, Swami S, Feldman D. The potential therapeutic benefits of vitamin D in
the treatment of estrogen receptor positive breast cancer. Steroids, 2012; 77(11): 1107-12.
9. Vu D, Sakharkar P, Tellez-Corrales E, Shah T, Hutchinson I, Min DI. Association of
vitamin D binding protein polymorphism with long-term kidney allograft survival in
Hispanic kidney transplant recipients. Mol Biol Rep, 2013; 40(2): 933-939.
doi:10.1007/s11033-012-2134-6. Epub 2012 Oct 17.
10. Vu D, Corrales E, Sakharkar P, Kissen MS, Shah T, Hutchinson I, Min DI. Impact of NF-
κB gene polymorphism on allograft outcome in Hispanic renal transplant recipients.
Transpl Immunol, 2013; 28(1): 18–23. Published online 2012 Nov 12.
doi: 10.1016/j.trim.2012.11.001.
11. Vu D, Sakharkar P, Shah T, Naraghi R, Yasir Q, Hutchinson I, Min DI. Association of
interferon gamma gene polymorphisms with BK virus infection among Hispanic renal
allograft recipients. Transplantation, 2014; 97(6): 660-667. doi:
10.1097/01.TP.0000438115.20198.89.
12. Vu D, Shah T, Ansari J, Sakharkar P, Yasir Q, Naraghi R, Hutchinson I, Min
DI. Interferon-gamma gene polymorphism +874 A/T is associated with an increased risk
of cytomegalovirus infection among Hispanic renal transplant recipients. Transpl Infect
Dis, 2014; 16: 724–732. DOI: 10.1111/tid.12285.

www.wjpps.com Vol 6, Issue 7, 2017.
1094
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
13. Mitra S, Desai M,Khatkhatay MI. Vitamin D receptor gene polymorphism and bone
mineral density in postmenopausal Indian women. Maturitas, 2006; 55(1): 27-35.
14. Amanzholkyzy A, Nurgalieva R, Dosimov A, Stankevicius E, Kaldybaeva A. Ethnic
Manifestations of Gene Polymorphisms of Vitamin D Receptor (VDR) in Adolescents of
Western Kazakhstan Region. J Natl Med Assoc, 2017.
DOI: http://dx.doi.org/10.1016/j.jnma.2017.02.012.
15. Hauache, O., Lazaretti-Castro, M., Andreoni, S. et al. Vitamin D Receptor Gene
Polymorphism: Correlation with Bone Mineral Density in a Brazilian Population with
Insulin-Dependent Diabetes Mellitus. Osteoporos Int, 1998; 8: 204.
doi:10.1007/s001980050055.
16. Nelson DA, Vande Vord PJ, Wooley PH. Polymorphism in the vitamin D receptor gene
and bone mass in African-American and white mothers and children: a preliminary
report. Ann Rheum Dis, 2000; 59: 626-630.
17. Kung AWC, Yeung SSC, Lau KS. Vitamin D Receptor Gene Polymorphisms and Peak
Bone Mass in Southern Chinese Women. Bone, 1998; 22(4): 389-393.
18. Cheung K, Chan D, Karppinen J, et al. Association of the Taq I Allele in Vitamin D
Receptor with Degenerative Disc Disease and Disc Bulge in a Chinese Population. Spine,
2006; 31(10): 1143-1148.
19. S K Lim, Y S Park, J M Park, Y D Song, E J Lee, K R Kim, H C Lee, K B Huh; Lack of
association between vitamin D receptor genotypes and osteoporosis in Koreans. J Clin
Endocrinol Metab, 1995; 80(12): 3677-3681. doi: 10.1210/jcem.80.12.8530619.
20. Fischer PR, Thacher TD, Pettifor JM, Jorde LB, Eccleshall TR, Feldman D. Vitamin D
Receptor Polymorphisms and Nutritional Rickets in Nigerian Children. J Bone Miner
Res, 2000; 15: 2206–2210.
21. Hou, MF., Tien, YC., Lin, GT. et al. Association of vitamin D receptor gene
polymorphism with sporadic breast cancer in Taiwanese patients. Breast Cancer Res
Treat, 2002; 74(1): 1-7. doi:10.1023/A:1016048900049.
22. Lavin PJ, Laing ME, O'Kelly P, Moloney FJ, Gopinathan D, Al Aradi A, et al. Improved
Renal Allograft Survival with Vitamin D Receptor Polymorphism. Ren Fail, 2007; 29(7):
785-789. DOI: 10.1080/08860220701540417.
23. Min D, Vu D, Tellez-Corrales E, Yang J, Sakharkar P, Shah T, Hutchinson I.
Polymorphism of the Vitamin D Receptor and Risk of New-Onset Diabetes after
Transplantation in Hispanic Kidney Transplant Recipients [abstract]. Am J Transplant,
2013; 13 (suppl 5). Available at: http://atcmeetingabstracts.com/abstract/polymorphism-

www.wjpps.com Vol 6, Issue 7, 2017.
1095
Chauhan et al. World Journal of Pharmacy and Pharmaceutical Sciences
of-the-vitamin-d-receptor-and-risk-of-new-onset-diabetes-after-transplantation-in-
hispanic-kidney-transplant-recipients/. Accessed May 29, 2017.
24. Yao X, Zeng H, Zhang G, et al. The Associated Ion between the VDR Gene
Polymorphisms and Susceptibility to Hepatocellular Carcinoma and the
Clinicopathological Features in Subjects Infected with HBV. Biomed Res Int, 2013;
Article ID 953974. 8 pages. doi:10.1155/2013/953974.
25. Tachi Y, Shimpuku H, Nosaka Y, et al. Vitamin D receptor gene polymorphism is
associated with chronic periodontitis. Life Sci, 2003; 73(26): 3313-3321.