Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals

de Oliveira, R; Cerda A.; Genvigir, FD; Sampaio, MF; Armaganijan D.; Bernik, MMS; Dorea, EL; Hirata, MH; Hinuy, HM; Hirata, RDC

Abstract

Objective: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. Subjects and methods: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G> A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. Results: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95% CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). Conclusions: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

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Título según WOS: Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals
Título de la Revista: ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA
Volumen: 57
Número: 9
Editorial: SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA
Fecha de publicación: 2013
Página de inicio: 677
Página final: 684
Idioma: English
Notas: ISI