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Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil

Abstract

OBJECTIVE: To investigate associations of polymorphisms in the LEP, LEPR and NPY genes with obesity-related traits in a Brazilian population of European descent.

METHODS: A total of 183 women and 153 men (mean body mass index (BMI), 26.1±4.8 kg/m2) were genotyped using the PCR-RFLP procedure for the LEP A19G, LEPR Gln223Arg, LEPR PRO1019pro and NPY Leu7Pro polymorphisms. Frequencies were compared among normal-weight and overweight plus obese groups with chi-square tests, mean BMI and waist circumference were compared among genotypes by t-tests and analysis of variance.

RESULTS: The genotype and allele frequencies of the LEPR Gln223Arg polymorphism were significantly different between normal-weight and overweight plus obese groups (P=0.013 and 0.009, respectively). Although there was no difference in the mean adjusted BMI among the three LEPR Gln223Arg genotypes, a trend was observed for Arg/Arg individuals to have a higher mean BMI compared to Gln/Gln homozygotes, with heterozygote individuals presenting intermediate mean BMI between the two homozygote groups (ANOVA, P=0.063). However, in non-smokers, the LEPR Gln223Arg polymorphism showed a highly significant effect over BMI (P=0.009). When the analysis was restricted to premenopausal women, a highly significant effect of NPY was observed. Women bearing the Pro variant presented a lower BMI than wild-type homozygotes (P=0.001).

CONCLUSION: Our findings suggest that genetic variability in the leptin receptor and neuropeptide Y genes is implicated in body weight regulation, the LEPR Gln223Arg variant being associated with a BMI increase in this Caucasian population, especially in non-smokers, while the NPY Leu7Pro polymorphism was associated with BMI reduction in premenopausal women.

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Acknowledgements

Thanks are due to Ana Lúcia S Antunes and Maria Perpetua de Oliveira Pinto from the Clinical Analysis Laboratory of the Pharmacy College of Federal University of Rio Grande do Sul and to Fabiana M de Andrade, Marilu Fiegenbaum, Silvana de Almeida and Marcel Arsand for help in the sample collection. Financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Programa de Apoio a Núcleos de Excelência (PRONEX, Brazil) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil).

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Mattevi, V., Zembrzuski, V. & Hutz, M. Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil. Int J Obes 26, 1179–1185 (2002). https://doi.org/10.1038/sj.ijo.0802067

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