Lack of association between the G-2548A polymorphism of the leptin gene and psoriasis in a Turkish population.
ABSTRACT Psoriasis is a multifactorial disease in which genetic and inflammatory factors play important roles. Leptin is classified as a cytokine and plays an important role in the regulation of the T-helper response. A common polymorphism in the promoter of the human leptin gene (G-2548A) may have a role in the pathogenesis of psoriasis.
To investigate the association between psoriasis and leptin gene polymorphism (G-2548A).
The study involved 109 patients with psoriasis and 125 healthy controls. Analyses of G-2548A polymorphism of the leptin gene were made by the polymerase chain reaction-restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin gene G-2548A) and alleles (G and A) were scored and the frequencies were estimated. The frequencies of alleles and genotypes in patients and controls were compared. The relationship between leptin gene polymorphism and the clinical features of the patients was analyzed.
Both genotype [odds ratio (OR), 0.921; 95% confidence interval (CI), 0.501-1.694; P = 0.792] and allele (OR, 0.864; 95% CI, 0.600-1.242; P = 0.429) frequencies were not significantly different between patient and control groups. In addition, there was no significant association between genotype and allele frequencies and the clinical characteristics of psoriasis.
In this case-control study, no evidence of association between the G-2548A variant of the leptin gene and psoriasis was found.
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ABSTRACT: We investigated the relationship between eight polymorphisms in the gene encoding for vascular endothelial growth factor (VEGF) (-1540C > A, -1512Ins18, -1451C > T, -460T > C, -160C > T, -152G > A, -116G > A and +405G > C) and plaque-type psoriasis stratified for age at onset, gender and family history of dermatosis. For this purpose, 117 patients with chronic plaque-type psoriasis and 215 healthy subjects were enrolled. We found that being homozygous -1540AA, -1512InsIns, -1451TT, -460CC and -152AA conferred a significant risk in developing psoriasis compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and -152AG) and homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and -152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively]. Conversely, having the -116AA or +405GG genotype did not significantly increase the risk of disease expression compared with other genotypes of the same loci. Interestingly, we found that -1540AA, -1512InsIns, -1451TT, -460CC and -152AA homozygous genotypes have a significant two-fold increased risk in developing psoriasis after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19, 2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as compared with controls. On the contrary, we found no phenotype-genotype association of the same magnitude among the patients in whom psoriasis developed at or before the age of 40 years (early-onset psoriasis) compared with controls. Genotype distributions were not significantly different when cases and controls were stratified either by gender or family history of psoriasis. Finally, VEGF plasma concentration was not significantly different between patients and controls and was not correlated with the severity of the disease.Experimental Dermatology 05/2006; 15(5):368-76. · 3.58 Impact Factor
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ABSTRACT: The mouse ob mutation has been mapped relative to a series of RFLPs among the progeny of three separate mouse crosses: an intraspecific backcross, an intraspecific intercross, and an interspecific intercross. Genotypic assignment at the ob locus was made by making use of measurements of body mass index and the plasma concentrations of glucose and insulin. These data have suggested that the development of diabetes in these animals is a consequence of unlinked polygenes. There was also evidence that unlinked Mus spretus alleles can diminish the obesity of mice. From these data we have mapped several markers on chromosome 6 with the following order: cen-Cola-2-Met-ob-Cpa-Tcrb. The homologs of markers that flank ob map to human chromosome 7q, suggesting that if there is a human homologue of ob, it maps to 7q31.Genomics 01/1992; · 3.01 Impact Factor
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ABSTRACT: To investigate associations of polymorphisms in the LEP, LEPR and NPY genes with obesity-related traits in a Brazilian population of European descent. A total of 183 women and 153 men (mean body mass index (BMI), 26.1+/-4.8 kg/m(2)) were genotyped using the PCR-RFLP procedure for the LEP A19G, LEPR Gln223Arg, LEPR PRO1019pro and NPY Leu7Pro polymorphisms. Frequencies were compared among normal-weight and overweight plus obese groups with chi-square tests, mean BMI and waist circumference were compared among genotypes by t-tests and analysis of variance. The genotype and allele frequencies of the LEPR Gln223Arg polymorphism were significantly different between normal-weight and overweight plus obese groups (P=0.013 and 0.009, respectively). Although there was no difference in the mean adjusted BMI among the three LEPRGln223Arg genotypes, a trend was observed for Arg/Arg individuals to have a higher mean BMI compared to Gln/Gln homozygotes, with heterozygote individuals presenting intermediate mean BMI between the two homozygote groups (ANOVA, P=0.063). However, in non-smokers, the LEPR Gln223Arg polymorphism showed a highly significant effect over BMI (P=0.009). When the analysis was restricted to premenopausal women, a highly significant effect of NPY was observed. Women bearing the Pro variant presented a lower BMI than wild-type homozygotes (P=0.001). Our findings suggest that genetic variability in the leptin receptor and neuropeptide Y genes is implicated in body weight regulation, the LEPR Gln223Arg variant being associated with a BMI increase in this Caucasian population, especially in non-smokers, while the NPY Leu7Pro polymorphism was associated with BMI reduction in premenopausal women.International Journal of Obesity 10/2002; 26(9):1179-85. · 5.22 Impact Factor
© 2007 The International Society of DermatologyInternational Journal of Dermatology 2007,
play important roles. Leptin is classified as a cytokine and plays an important role in the
regulation of the T-helper response. A common polymorphism in the promoter of the human
leptin gene (G-2548A) may have a role in the pathogenesis of psoriasis.
To investigate the association between psoriasis and leptin gene polymorphism
The study involved 109 patients with psoriasis and 125 healthy controls. Analyses of
G-2548A polymorphism of the leptin gene were made by the polymerase chain reaction-
restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin
gene G-2548A) and alleles (G and A) were scored and the frequencies were estimated. The
frequencies of alleles and genotypes in patients and controls were compared. The relationship
between leptin gene polymorphism and the clinical features of the patients was analyzed.
Both genotype [odds ratio (OR), 0.921; 95% confidence interval (CI), 0.501–1.694;
P = 0.792] and allele (OR, 0.864; 95% CI, 0.600–1.242;
significantly different between patient and control groups. In addition, there was no significant
association between genotype and allele frequencies and the clinical characteristics of
In this case–control study, no evidence of association between the G-2548A
variant of the leptin gene and psoriasis was found.
Psoriasis is a multifactorial disease in which genetic and inflammatory factors
P = 0.429) frequencies were not
Blackwell Publishing LtdOxford, UKIJDInternational Journal of Dermatology0011-9059© 2007 The International Society of DermatologyXXX
Lack of association between the G-2548A polymorphism of the
leptin gene and psoriasis in a Turkish population
Psoriasis and leptin gene polymorphismKara et al.REPORT
M. Tayyar Canturk,
, Fatma Aydin,
, Hasan Bagci,
, Nilgün Senturk,
, Yüksel Bek,
, Sezgin Gunes,
, and Ahmet Yasar Turanli,
From the Departments of Medical Biology and
Genetics, Dermatology, and Biostatistics,
Ondokuz Mayis University, Samsun, Turkey
Department of Medical Biology and Genetics
Ondokuz Mayis University
Psoriasis is a chronic inflammatory disorder of the skin in
which both genetic and immunologic factors play a key
Several studies have documented the role of the T-
helper-1 (Th1) response in psoriasis. The majority of leuko-
cytes in the dermis in psoriasis are CD4-positive T-helper
lymphocytes of the Th1 phenotype. The response of psoriasis
to drugs that block T-cell activation, migration, or cytokine
secretion, and the central role played by activated T cells,
have been studied in animal model systems.
cytokines are overexpressed in psoriatic lesions and are
responsible for the communication between various cells.
The cytokine network is crucial in the control of epidermal
proliferation, differentiation, and inflammation. It has been
shown that cytokines from T lymphocytes can induce
epidermal cells to release interleukin-8 (IL-8).
On the basis of pedigree analyses, a polygenic inheritance
provides the best model for the genetics of psoriasis. Population-
based studies have revealed that psoriasis is associated with
human leukocyte antigen (HLA) genes class I and II, located
on chromosome 6. HLA-Cw*0602 gene carriers show the
highest risk of development of psoriasis.
Using linkage techniques in psoriasis families, several psoriasis
susceptibility loci have been mapped: PSORS1, PSORS2
), PSORS3 (
), PSORS4, PSORS5 (
PSORS6, PSORS7 (
), and PSORS9 (
6p21, 17q, 4q, 1cen-q21, 3q21, 19p, 1p, and 4q31, respectively.
The loci on 6p and 17q appear to be well established.
The leptin (
) gene, the human homolog of the rat obese
) gene, has been cloned and sequenced by Zhang
is located at 7q31.3 and expresses a 4.5-kb mRNA in adipose
Both the structure of leptin and that of its receptor
suggest that leptin should be classified as a cytokine. It is
known that leptin is influenced by proinflammatory cytokines;
patients with an acute-phase response have significantly higher
serum leptin levels. Leptin increases IL-2 and interferon-
) production and decreases IL-4 levels. Thus, leptin
may play an important role in the regulation of the T-helper
(Th1/Th2) balance towards the Th1 type.
International Journal of Dermatology 2007,
, 1271–1274© 2007 The International Society of Dermatology
Psoriasis and leptin gene polymorphismKara et al.
Several studies have reported correlations of different
variations throughout the length of the
promoter, noncoding, and coding regions, with different
The single nucleotide polymorphism (SNP)
A) in the 5
flanking region at –2548 has been shown
to be involved in
gene regulation. Higher mRNA expression
and serum leptin levels have been observed in AA genotype
As psoriasis is a multifactorial disease with both a genetic
and immunologic background, with a Th1-type immune
response, and leptin has been shown to play a role in this
process, we aimed to investigate whether this functional
polymorphism (G-2548A) of the
genetic predisposition for psoriasis.
gene, such as
gene is involved in the
Materials and Methods
One hundred and nine patients with psoriasis and 125 healthy
controls were included in this study. Patients were recruited from
the Dermatology Department at Ondokuz Mayis University Hospital,
Samsun, Turkey. The diagnosis of psoriasis was established by
clinical and histopathologic examination. The study was approved
by the ethics committee of Ondokuz Mayis University, and informed
consent was obtained from all subjects. All patients and controls
were unrelated individuals from the northern region of Turkey.
For all patients and healthy controls, the age, sex, and family
history for psoriasis were recorded. The genotypes (GG, GA, and
AA of leptin G-2548A) and alleles (G and A of leptin –2548) were
scored. The frequency of the G-2548A variant was compared
between the two groups. The presence of the A allele (GA + AA)
was regarded as a risk factor. The relationship between
polymorphism and the clinical features of psoriasis was also
Venous blood (5 mL) was obtained from all patients and controls.
Genomic DNA was isolated from peripheral blood leukocytes
by a standard salting-out extraction method. The G-2548A
polymorphism of the LEP gene was analyzed by polymerase
chain reaction (PCR) amplification. The presence of the G-2548A
variant was determined in all subjects by PCR-restriction fragment
length polymorphism analysis. A pair of primers [5
used to amplify the 241-bp fragment that includes the G-2548A
mutation site. The amplified PCR products were digested with
the restriction enzyme CfoI as recommended by the supplier
(Fermentas [Lithuania], Promega [Madison, WI, USA]). DNA
fragments were separated by electrophoresis on a 2.5% agarose
gel. In the presence of nucleotide A, the 241-bp PCR product is not
cut while in the presence of nucleotide G, the PCR into 205-bp and
36-bp fragments with CfoI.
(sense) and 5
Statistical analyses were performed using SPSS 13.0 for
Windows, release 13.01 (license code 9071653). The proportions
of the alleles and genotypes were compared between patients and
controls using a nonparametric test (
confidence interval, 95% CI). A P
considered to be statistically significant.
; odds ratio, OR; 95%
value of 0.05 or less was
The control group consisted of 56 men (44.8%) and 69
women (45.2%) with a mean age of 38.9 ± 6.36 years. The
patient group consisted of 55 men (50.5%) and 54 women
(49.5%) with a mean age of 43.2 ± 15.0 years. The mean age
of onset of psoriasis was 31.3 ± 16.5 years.
The genotype distribution and allele frequencies for the
G-2548A polymorphism in psoriasis patients and con-
trols are presented in Table 1. In addition, the correlations
between the genotype and allele frequencies and the clinical
characteristics are presented in Table 2. Both genotype (OR,
0.921; 95% CI, 0.501–1.694;
0.864; 95% CI, 0.600–1.242;
not significantly different between the patient and control
groups. In addition, there was no significant association between
genotype and allele frequencies and clinical characteristics
(Table 2). In this case–control study, we found no evidence of
association between the G-2548A variant of the
and psoriasis in a Turkish population.
= 0.792) and allele (OR,
= 0.429) frequencies were
Table 1 Genotype and allele frequencies for psoriasis and control groups
(n = 109)
(n = 125)
χ χ χ χ2
GA + AA
58 + 25 = 83
61 + 36 = 97
CI, confidence interval; OR, odds ratio.
© 2007 The International Society of Dermatology International Journal of Dermatology 2007,
Kara et al.Psoriasis and leptin gene polymorphism
Psoriasis is defined as a complex, multigenic, multifactorial
disease, whose manifestations are determined by a combination
of certain genes as well as by various environmental triggering
Several studies have examined the relationship between
gene polymorphisms and psoriasis. According to Campalani
., the frequency of the Apo e4 allele (+3937C/+4075C)
is significantly higher in patients with chronic plaque psoriasis
and guttate psoriasis than in controls (
respectively); however, there is no significant difference in
allele frequency between patients with palmoplantar pustulosis
examined the distribution of three cytotoxic
T-lymphocyte-associated antigen-4 SNPs (–1147C/T, –318C/
T, and +49A/G) in 116 patients with psoriasis and 123
healthy blood donors. For all three SNPs, the frequencies
of alleles, genotypes, and three-point haplotypes were very
similar in patients and controls, suggesting no contribution of
these genetic variants to psoriasis.
investigated the relationship between eight
polymorphisms in the gene encoding for vascular endothelial
growth factor (–1540C
A, –1512 Ins18, –1451C
C) and plaque-type psoriasis stratified for age at
onset, gender, and family history of dermatosis. Genotype
distributions were not significantly different between cases
Genetic mutations in the
leptin receptor (
) gene in db/db mice produce a phenotype
characterized by morbid obesity and immune dysfunction.
In humans, several polymorphisms linked to the obese
have been identified in the
genes: an A to G nucleotide change at position 19 in the 5
and a G to A substitution at nucleotide
gene of ob/ob mice and in the
–2548 upstream of the ATG start site,
gene, and an A to G transition at nucleotide 668, resulting in
a glutamine to arginine substitution at codon 223 (Q223R),
gene. This glutamine to arginine substitution
occurs within the first of two putative leptin-binding regions
and may be associated with impaired
Enhanced gene expression and increased circulating leptin
levels have been reported in those with the
–2548 AA genotypes,
variant has been reported to confer lower plasma leptin levels
in morbidly obese women. The leptin G-2548A polymor-
phism has been found to be related to immune dysfunction in
obesity and non-Hodgkin’s lymphoma.
We studied the possible association between the
G-2548A polymorphism and psoriasis in a northern Turkish
population. Our findings indicate that both genotype and
allele frequencies do not differ significantly between patient
and control groups. In addition, there is no significant associ-
ation between genotype and allele frequencies and clinical
In conclusion, our results indicate that the G-2548A
polymorphism in the promoter region of the
associated with psoriasis in a northern Turkish population.
This is the first report of its kind from Turkey; therefore,
further studies are warranted to confirm our results.
both in the
gene is not
This study was financially supported by Ondokuz Mayis
University Research Foundation (T-370).
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Table 2 Correlation of GA + AA and GG genotypes with the
(n = 109)
GGGA + AA
Family history of psoriasis
*Other: guttate, palmoplantar, palmoplantar pustular,
generalized pustular, scalp psoriasis.
International Journal of Dermatology 2007, 46, 1271–1274 © 2007 The International Society of Dermatology
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