The rs2167270 polymorphism of leptin gene is associated with atopic dermatitis.
ABSTRACT: Atopic dermatitis is a chronic inflammatory skin disease that arises because of complex environmental, immunological, and genetic interactions. Adipokines are bioactive mediators secreted from adipocytes of white adipose tissue and are known to have a role in body metabolism and regulation of immune responses. Leptin is a proinflammatory adipokine that functions mainly to regulate food intake and energy expenditure. Few studies have implicated adipokines in the pathogenesis of atopic dermatitis. In this study, we investigated the association of three leptin gene polymorphisms: -2548G>A (rs7799039), -188 C/A (rs791620), and A19G (rs2167270), with the incidence of atopic dermatitis. One hundred and sixty-four patients and one hundred and sixty-seven age- and gender-matched controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism procedure. A significant association was found between rs2167270 and the incidence of atopic dermatitis (P < 0.05). The GG allele was more prevalent in the patients' group with genotype frequency of 38.7%, compared to 26.1% for the control group. No significant differences were found in the genotype distribution or allelic frequency of the other two examined polymorphisms, rs7799039 and rs791620, between atopic dermatitis patients and controls (P > 0.05). The results suggest that rs2167270 might play a role in the pathogenesis of atopic dermatitis.
Project description:Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98?ng/mL) than those with AG genotype (10.07 ± 0.60?ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59?ng/mL) than the subjects with GG genotype (9.52 ± 0.79?ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516-90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161-12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426-20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness.
Project description:INTRODUCTION:Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD. METHODS:We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system. RESULTS:The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males. CONCLUSIONS:The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.
Project description:BACKGROUND:Adipose tissue is an important endocrine organ that secretes a number of adipokines, such as adiponectin (ADIPOQ), leptin (LEP), leptin receptor (LEPR), and resistin (RETN) which may be implicated in obesity. Some adipokines' polymorphisms of genes might influence their concentrations and/or activities. Our aim was to study the relationship between seven SNPs in ADIPOQ (+45T<G (rs2241766); +276G<T (rs1501299); -4255C<T (rs822393); -395G<T (rs17366568)), LEP (2548G<A (rs7799039)), LEPR (223Q<R (rs1137101)), and RETN (-420C<G (rs1862513)) and obesity in Hammam Sousse Sahloul Heart Study (HSHS). METHODS:The study, carried out between February and June 2009, is mainly focused on 1121 respondents in HSHS which is a population-based epidemiological study of type "community-based" on cardiovascular risk. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum lipids and anthropometric parameters were measured. Statistic analysis was performed on SPSSv19. RESULTS:The polymorphisms of ADIPOQ 4522C<T and 276G<T, LEP 2548G<A, and RETN 420C<G seem to contribute to obesity. In fact, adjusted odds ratios (ORs) of obesity associated with mutated genotypes of each polymorphism were respectively OR=1.38, P=.037; OR=0.608, P<.001; OR=2.23, P=.034; and OR=2.18, P<.001. The 276G<T, 4522C<T, and 420C<G were associated with increased BMI (P=.010, P=.028, and P<.001). A significant association was found between the 276G<T; 4522C<T, LEP 2548G<A and 420C<G, and the waist circumference and hip measurements. CONCLUSION:ADIPOQ, LEP, and RETN gene polymorphisms were associated with obesity parameters in HSHS population.
Project description:The revelation of leptin action mechanisms has led to various attempts to establish the association of polymorphisms in the leptin gene with obesity-related phenotypes. But, outcomes have been contradicting, which made the information on the role of the leptin gene in regulating the mechanism of pathophysiology of obesity inexplicable. Moreover, none of the studies are known to have similar implications on the Indian population. To address such contradictions, our study aims to evaluate the association of leptin gene polymorphism with obesity and leptin levels in a South Indian Population. A total of 304 cases (BMI?27.5) and 309 controls (BMI?23) from local inhabitants of Mysore, Karnataka were recruited for the study. The leptin gene variants rs7799039, rs2167270 and rs4731426 independently, as well as in 4 haplotype combinations, were found to be significantly associated with the risk of obesity. An increasing trend in BMI and leptin levels was observed with every addition of A and C minor alleles of exonic variant (rs2167270) and intronic variant (rs4731426) respectively. However, only AA genotype of SNP rs7799039 was positively associated with BMI. None of the SNPs were associated with fat percentage and waist to hip ratio. On a whole, this data suggests that the common polymorphisms in the leptin gene are strong predictors of obesity and leptin levels in South Indians.
Project description:Leptin may play an important role in colorectal cancer because of its role in energy balance, insulin and inflammation. We evaluated the LEP rs2167270 (19 G > A) and rs7799039 (-2548 G > A) polymorphisms and the leptin receptor, LEPR rs6588147 (located in intron 2), polymorphism with risk of developing colon cancer in a study of 1,567 cases and 1,965 controls. We evaluated the effects of the polymorphisms with body mass index (BMI), recent use of aspirin/NSAIDs and genetic variations in genes related to insulin signaling pathways including insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and insulin-related substrates 1 and 2 (IRS1, IRS2) and the vitamin D receptor (VDR). We observed a slight reduction in colon cancer risk with the AA LEP rs2167270 genotype (OR 0.79 95% CI 0.64, 0.98) and although not reaching statistical significance, with the combined GG LEP rs2167270 and GG LEPR rs6588147 (OR 0.70, 95% CI 0.49, 1.02) genotypes. BMI did not interact with any of these polymorphisms to alter colon cancer risk. However, recent aspirin/NSAID use significantly interacted with both LEP polymorphisms. Likewise, variants of IGF1 and IRS2 interacted with the LEP rs2167270 polymorphism. VDR polymorphisms interacted with all LEP and LEPR polymorphisms. These data support an association between LEP and colon cancer. They also suggest that the mechanisms linking leptin to colon cancer may be independent of energy balance.
Project description:Background:Leptin (LEP) and LEP receptor (LEPR) polymorphisms may be associated with the development of cancer. Methods:In this study, we selected five functional LEP and LEPR single-nucleotide polymorphisms (SNPs) and conducted a case-control study to determine the relationship of LEP and LEPR polymorphisms with hepatocellular carcinoma (HCC) risk in Eastern Chinese Han population. There were 584 HCC cases and 923 cancer-free controls included in our study. HCC patients and controls were fully matched by age and sex. SNPscan™ genotyping method was used to analyze the genotyping of LEP rs2167270 G>A, rs7799039 A>G, LEPR rs6588147 G>A, rs1137100 G>A, and rs1137101 G>A SNPs. Results:We found that LEP rs7799039 A>G and rs2167270 G>A polymorphisms were associated with the susceptibility of HCC in this population (LEP rs7799039 A>G: GG vs AA: adjusted odds ratio [OR]=2.03, 95% CI, 1.22-3.38, P=0.006 and GG vs AA/AG: adjusted OR=1.97, 95% CI, 1.20-3.22, P=0.007; rs2167270 G>A: AA vs GG: adjusted OR=2.03, 95% CI, 1.10-3.75, P=0.024 and AA vs GG/GA: adjusted OR=2.01, 95% CI, 1.10-3.68, P=0.023). However, LEPR rs6588147 G>A polymorphism decreased the risk of HCC (GA vs GG: adjusted OR=0.62, 95% CI, 0.45-0.86, P=0.005 and AA/GA vs GG: adjusted OR=0.64, 95% CI, 0.47-0.88, P=0.007). Conclusion:This case-control study highlights that LEP rs7799039 A>G and rs2167270 G>A polymorphisms increase the susceptibility to HCC; however, LEPR rs6588147 G>A polymorphism may be a protective factor for HCC in Eastern Chinese Han population.
Project description:BACKGROUND:Obesity has become the main health issue in developed countries as it impacts life expectancy and increases mortality of cerebrovascular or cardiovascular diseases. The leptin is one of the adipokines which presents in the serum in proportion to the amount of adipose tissue and is translated from LEP gene. It involves in energy homeostasis, lipid and glucose metabolisms, modulation of immune systems, and thermogenesis. Many previous studies have revealed controversial results between LEP polymorphisms and leptin levels in different ages and ethnicities. Herein, we investigated the impacts of LEP polymorphism against leptin levels in Taiwanese subjects. METHODS:In 599 Taiwanese subjects, excluding clinically overt systemic disease, age below 18 years old, and C-reactive protein (CRP) level of above 10 mg/L, few of LEP polymorphisms were genotyped with TaqMan SNP genotyping assays, were further analyzed for association with leptin level in univariate and multivariate linear regression analyses with Bonferroni correction for multiple tests in stratified groups. The univariate and stepwise multivariate linear regression analyses were performed to determine the coefficient of determinant of LEP polymorphisms over leptin level. RESULTS:Significant associations were found between LEP polymorphisms and leptin levels in obese women. Circulating leptin level was positively correlated with inflammatory, insulin resistance markers, and visceral obesity markers in all subjects. Furthermore, stratified and interaction analyses revealed that LEP polymorphisms, rs7799039 and rs2167270, were significantly associated with leptin levels in obese women-8%-10% of which could be explained by LEP polymorphisms. CONCLUSION:The LEP polymorphisms are independently associated with leptin levels in Taiwanese obese women. Further, the genetic determinants for leptin levels may be different between obese and nonobese, and in different sex individuals. The obesity status and female sex may exert modification effect on transcription of LEP, particularly in obese women.
Project description:BACKGROUND: Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP) may be associated with markers of CKD in indigenous black Africans. METHODOLOGY/PRINCIPAL FINDINGS: Black South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482). CONCLUSIONS/SIGNIFICANCE: These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.
Project description:To investigate potential associations between the histamine N-methyltransferase (HNMT) gene, HNMT, C314T (Thr105Ile) polymorphism and atopic dermatitis in a cohort of Caucasian children.Prospective, multicenter, genotype-association study.Four academic, tertiary care medical centers within the Pediatric Pharmacology Research Unit network.Two hundred forty-nine Caucasian children aged 6 months-5 years with atopic dermatitis (127 patients) or without (122 control subjects).Buccal swabs (one swab/cheek) were performed to obtain epithelial cells for extraction of genomic DNA.Data were collected on severity of atopic dermatitis, oral antihistamine treatment, and treatment response through parental report. The HNMT genotypes were successfully obtained in 116 control subjects and 122 patients with atopic dermatitis. Frequencies of the T314 variant allele (0.12 vs 0.06, p=0.04) and combined CT/TT genotype (0.24 vs 0.12, p=0.02) were significantly higher in children with atopic dermatitis compared with control subjects. Children with genotypes conferring reduced HNMT activity were 2 times more likely to have atopic dermatitis than those who were homozygous for the C314 reference allele.Increased histamine levels in patients with atopic dermatitis may result, at least in part, from reduced enzymatic inactivation via HNMT. Genetically associated reduction in histamine biotransformation may therefore contribute to the pathogenesis, persistence, and progression of atopic dermatitis. If confirmed, these data indicate that HNMT genotype might represent a common risk factor for development of atopic dermatitis, asthma, and allergic rhinitis and may be useful in identifying individuals who are candidates for early preventive pharmacotherapeutic intervention. Additional longitudinal studies will be required to assess the relationship between genotype, disease severity, and antihistamine response.
Project description:This systematic review aims to evaluate the association of adiponectin (ADIPOQ) and leptin (LEP) gene variants with energy intake. Cross-sectional, cohort, and case?control studies that reported an association of leptin and/or adiponectin gene variants with energy intake were included in this review. Human studies without any age restrictions were considered eligible. Detailed individual search strategies were developed for each of the following bibliographic databases: Cochrane, Latin American and Caribbean Center on Health Sciences Information (LILACS), PubMed/MEDLINE, Scopus, and Web of Science. Risk of bias assessment was adapted from the Downs and Black scale and was used to evaluate the methodology of the included studies. Seven studies with a pooled population of 2343 subjects were included. The LEP and ADIPOQ gene variants studied were LEP-rs2167270 (k = 1), LEP-rs7799039 (k = 5), ADIPOQ-rs2241766 (k = 2), ADIPOQ-rs17300539 (k = 1), and ADIPOQ marker D3S1262 (k = 1). Two of the seven studies reviewed demonstrated a positive association between the LEP-rs7799039 polymorphism and energy intake. Two other studies-one involving a marker of the ADIPOQ gene and one examining the ADIPOQ-rs17300539 polymorphism-also reported associations with energy intake. More research is needed to further elucidate the contributions of genetic variants to energy metabolism.