Dataset Information

Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women.

ABSTRACT: 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.

SUBMITTER: Duan DM

PROVIDER: S-EPMC7057123 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women.

Duan De-Min DM Jhang Jing-Yi JY Wu Semon S Teng Ming-Sheng MS Hsu Lung-An LA Ko Yu-Lin YL

Molecular genetics & genomic medicine 20200108 3

<h4>Background</h4>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 ...[more]

PMID: 31914480

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Project description:BACKGROUND:Metabolic syndrome is a cluster of metabolic risk factors including dyslipidemia, impaired glucose tolerance, hypertension and central obesity. BDNF (Brain-derived neurotrophic factor) and leptin have been implied in the energy homeostasis. The purposes of this study were to examine concentrations of leptin, BDNF and biochemical parameters in metabolic-syndrome subjects and healthy controls, and also to search for associations of leptin gene (LEP) G2548A, leptin receptor gene (LEPR) Gln223Arg, and BDNF gene (BDNF) Val66Met polymorphisms with leptin levels, BDNF levels and metabolic syndrome among Thais. METHODS:The case-controlled design was performed using 322 Thai volunteers (160 metabolic-syndrome subjects; 162 controls) during the health screening program. Metabolic syndrome was assessed by using the modified National Cholesterol Education Program, Adult Treatment Panel III criteria. The levels of leptin, BDNF, insulin, glucose and lipids were measured in samples. Genotyping of LEP G2548A, LEPR Gln223Arg and BDNF Val66Met was carried out using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS:Serum leptin levels were significantly higher in the metabolic-syndrome group than the control group (p < 0.01), but the BDNF difference between them was not significant. Significant associations of LEPR Gln223Arg polymorphism were found with leptin and glucose levels (p < 0.05), after adjusting for potential covariates. This LEPR polymorphism in the metabolic-syndrome group was also significantly more frequent than in the control group (p < 0.05). However, other gene polymorphisms, LEP G2548A and BDNF Val66Met, showed no significant relationship with leptin levels, BDNF levels or metabolic syndrome. CONCLUSION:These findings suggest leptin levels are linked with metabolic syndrome. LEPR Gln223Arg polymorphism impacted leptin concentrations, and this gene polymorphism may influence susceptibility to metabolic syndrome among Thais.

Project description:BackgroundThis study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak.MethodsConvenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations.ConclusionsThe LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL.

Dataset Information

Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women.

Publications

Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women.

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