Allelic variants of the Melanocortin 4 receptor (MC4R) gene in a South African study group

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Obesity is a global epidemic that results in significant morbidity and mortality. Mutations in the melanocortin 4 receptor (MC4R) gene, which codes for a G-protein-coupled receptor responsible for postprandial satiety signaling, have been associated with monogenic obesity. The prevalence of obesity is on the increase in South Africa, and it is hypothesized that mutations in MC4R are a contributing factor. The aim of this study was to perform a retrospective assessment of the relationship between allelic variants of MC4R and BMI in a South African study cohort. DNA was isolated from a demographically representative cohort of 297 individuals and the entire MC4R gene sequenced by Sanger sequencing. Eight previously reported MC4R variants were identified in 42 of the 297 (14.1%) study participants. The most frequently observed MC4R alleles were V103I (4.0%), I170V (1.5%), and I198I (1.2%), while the remaining five variants together constituted 1.18%. Five compound heterozygotes were also detected. Although MC4R variants were rare, the majority of variation was observed in individuals of Black African ancestry. No statistically significant associations with BMI were reported. Given that lifestyle interventions have limited success in decreasing obesity, there is an urgent need to perform large-scale population studies to further elucidate the molecular underpinnings of this disease.

Keywords:
Genotype–phenotype correlation; melanocortin 4 receptor; obesity; South Africa

Autoři: Murray Logan ^1,2; Maria-Teresa Van Der Merwe ³; Tyren M. Dodgen ^2,4; Renier Myburgh ^1,2; Arinda Eloff ^1,2; Marco Alessandrini ^1,2; Michael S. Pepper ^1,2,5,*
Působiště autorů: Department of Immunology, University of Pretoria, Pretoria, South Africa ¹; Faculty of Health Sciences, Institute for Cellular and Molecular Medicine, University of Pretoria, Pretoria, South Africa ²; Department of Endocrinology, University of Pretoria, Pretoria, South Africa ³; Department of Pharmacology, University of Pretoria, Pretoria, South Africa ⁴; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland ⁵
Vyšlo v časopise: Molecular Genetics & Genomic Medicine 2015; Early View(Early View)
Kategorie: Original Research
prolekare.web.journal.doi_sk: https://doi.org/10.1002/mgg3.180

© 2015 University of Pretoria. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Souhrn

Keywords:
Genotype–phenotype correlation; melanocortin 4 receptor; obesity; South Africa

Zdroje

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