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

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 rece ptor (LEPR) gene were related to obesity and body fat distribution phenotyp es, such as waist and hip circumferences and the amount of visceral and sub cutaneous fat. METHODS: Three known LEPR polymorphisms, Lys109Arg, Gln223Arg and Lys656Asn , were typed on genomic DNA of 280 overweight and obese women (body mass in dex (BMI) > 25), aged 18-60 y. General linear model (GLM) analyses were per formed 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 inc reased hip circumference (P = 0.03), total abdominal fat (P = 0.03) and sub cutaneous fat (P = 0.04) measured by CT scan. Total abdominal fat was also higher in Gln223Gln homozygotes (P = 0.04). Also in postmenopausal women, l eptin levels were higher in Lys109Lys homozygotes (P = 0.02). CONCLUSION: In conclusion, polymorphisms in the leptin receptor gene are as sociated with levels of abdominal fat in postmenopausal overweight women. S ince body fat distribution variables were adjusted for fat mass, these resu lts suggest that DNA sequence variations in the leptin receptor gene play a role in fat topography and may be involved in the predisposition to abdomi nal obesity.