37baa1f1-70df-4026-8b27-7e65235c2007
title
Tests of linkage and/or association of the  LEPR  gene polymorphisms with obesity phenotypes in Caucasian nuclear families.
ca9b2d85-4da9-40ba-90c6-4cc63de07efa
abstract
Genetic variations in the  leptin receptor  ( LEPR ) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the  LEPR  gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely  Lys109Arg (A/G) ,  Lys656Asn (G/C) ,  Pro1019Pro (G/A) , in the  LEPR  gene were analyzed. Significant linkage disequilibrium (0.394 < or = |D'| < or = 0.688, P < 0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for  Lys656Asn  with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the  Lys656Asn  site had, on average, 3.16% higher lean mass and 2.71% higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the  LEPR  gene polymorphisms contribute to variation in obesity phenotypes.