Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population.

Sook-Ha Fan,Yee-How Say

doi:10.1186/1880-6805-33-15

Abstract

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.

Highlights

This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene Leptin gene (LEP) (A19G and G2548A) and leptin receptor gene 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
The variant allele frequency (VAF) for all the SNPs except for LEP G2548A were higher than that reported by Liew et al [11] in a sample of Malaysian university students, which was conducted as part of a pilot study prior to the present research
In accordance with most previous studies, this study failed to find an association between the LEP A19G polymorphism and obesity as supported by findings in Finnish subjects [8], Italian obese patients [12], Brazilians of European descent [13], Caucasians [14], and an African tribal population group [15]

Summary

Introduction

This 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. One of the most important routes involved in regulating body weight and energy expenditure is the leptin-melanocortin signaling pathway. Upon leptin binding to its receptor, a LEPRb/Janus kinase 2 (JAK2) complex is formed, resulting in cross-phosporylation. The tyrosine residue, Tyr1138 on LEPRb is important for signal transducer and activator of transcription 3 (STAT3) activation, which activates suppressor of cytokine signaling 3 (SOCS3) expression. This leads to negative inhibition of leptin signaling through Tyr985 and additional sites on JAK2. Mitogen-activated protein kinase (MAPK) and insulin receptor substrate/ phosphatidyl-inositol 3’ kinase (PI3K) pathways can be activated following JAK2 phosphorylation [4]

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Results

Conclusion