Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women

Abstract

OBJECTIVE:Leptin is an adipocyte-secreted hormone involved in body weight regulation, acting through the leptin receptor, localised centrally in the hypothalamus as well as peripherally, amongst others on adipose tissue. The aim of this study was to evaluate whether polymorphisms in the leptin receptor (LEPR) gene were related to obesity and body fat distribution phenotypes, such as waist and hip circumferences and the amount of visceral and subcutaneous fat. METHODS: Three known LEPR polymorphisms, Lys109Arg, Gln223Arg and Lys656Asn, were typed on genomic DNA of 280 overweight and obese women (body mass index (BMI) b 25), aged 18 ± 60 y. General linear model (GLM) analyses were performed in 198 pre-and 82 postmenopausal women, adjusting the data for age and menopausal state, plus fat mass for the fat distribution phenotypes. RESULTS: No associations were found between the LEPR polymorphisms and BMI or fat mass. In postmenopausal women, carriers of the Asn656 allele had increased hip circumference (P 0.03), total abdominal fat (P 0.03) and subcutaneous fat (P 0.04) measured by CT scan. Total abdominal fat was also higher in Gln223Gln homozygotes (P 0.04). Also in postmenopausal women, leptin levels were higher in Lys109Lys homozygotes (P 0.02). CONCLUSION: In conclusion, polymorphisms in the leptin receptor gene are associated with levels of abdominal fat in postmenopausal overweight women. Since body fat distribution variables were adjusted for fat mass, these results suggest that DNA sequence variations in the leptin receptor gene play a role in fat topography and may be involved in the predisposition to abdominal obesity.

Association of leptin receptor polymorphism with insulin resistance

“…Interestingly, just like our population in this study, most of the positive associations of the R allele with obese or insulin-resistant phenotypes were observed in young (mean age , 30 years old) and healthy populations (14,16,19). In contrast, negative associations were found in postmenopausal women (17,18) or in pathological states, such as impaired glucose tolerance (17) or overfeeding (15). It is possible therefore that this polymorphism contributes to the initiation of the events leading to insulin resistance in a subset of subjects.…”

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

“…In literature, both alleles of these SNPs have been reported as risk alleles for type 2 diabetes and obesity, and a metaanalytic study reported nonsignificant associations. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]48 Consequently, additional studies in larger populations need to be carried out, to verify the involvement of these coding LEPR SNPs in the 'fetal insulin hypothesis'.…”

“…In this study we therefore examined the effect of common SNPs in LEP and LEPR on birth weight and adult metabolic risk factors for type 2 diabetes measured in young twins recruited from the East Flanders Prospective Twin Survey (EFPTS). The SNPs studied have previously been associated with type 2 diabetesrelated traits in other populations, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and are either nonsynonymous or located in a region that might be of importance in the regulation of gene expression.…”

Association studies of genetic polymorphisms in central obesity: a critical review

“…94 In postmenopausal women, carriers of the Asn656 allele had increased total abdominal fat measured by CT scan. 42 Total abdominal fat was also higher in Gln223Gln homozygotes. 42 In a population sample of Brazilian men of European descent, the Arg223Arg genotype was more frequent in subjects with a waist circumference equal or above 102 cm.…”

“…42 Total abdominal fat was also higher in Gln223Gln homozygotes. 42 In a population sample of Brazilian men of European descent, the Arg223Arg genotype was more frequent in subjects with a waist circumference equal or above 102 cm. 43 No differences in genotype frequencies among women with and without central obesity were observed.…”