title: Allelic variants of the Melanocortin 4 receptor (MC4R) gene in a South African study group.
abstract: 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.
authors.affiliation: Department of ImmunologyUniversity of PretoriaPretoriaSouth Africa; Faculty of Health SciencesInstitute for Cellular and Molecular MedicineUniversity of PretoriaPretoriaSouth Africa.
authors.forename: Murray
authors.initials: M
authors.lastname: Logan
authors.affiliation: Department of Endocrinology University of Pretoria Pretoria South Africa.
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Van der Merwe
authors.affiliation: Faculty of Health SciencesInstitute for Cellular and Molecular MedicineUniversity of PretoriaPretoriaSouth Africa; Department of PharmacologyUniversity of PretoriaPretoriaSouth Africa.
authors.forename: Tyren M
authors.initials: TM
authors.lastname: Dodgen
authors.affiliation: Department of ImmunologyUniversity of PretoriaPretoriaSouth Africa; Faculty of Health SciencesInstitute for Cellular and Molecular MedicineUniversity of PretoriaPretoriaSouth Africa.
authors.forename: Renier
authors.initials: R
authors.lastname: Myburgh
authors.affiliation: Department of ImmunologyUniversity of PretoriaPretoriaSouth Africa; Faculty of Health SciencesInstitute for Cellular and Molecular MedicineUniversity of PretoriaPretoriaSouth Africa.
authors.forename: Arinda
authors.initials: A
authors.lastname: Eloff
authors.affiliation: Department of ImmunologyUniversity of PretoriaPretoriaSouth Africa; Faculty of Health SciencesInstitute for Cellular and Molecular MedicineUniversity of PretoriaPretoriaSouth Africa.
authors.forename: Marco
authors.initials: M
authors.lastname: Alessandrini
authors.affiliation: Department of ImmunologyUniversity of PretoriaPretoriaSouth Africa; Faculty of Health SciencesInstitute for Cellular and Molecular MedicineUniversity of PretoriaPretoriaSouth Africa; Department of Genetic Medicine and DevelopmentFaculty of MedicineUniversity of GenevaGenevaSwitzerland.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
keywords: Genotype–phenotype correlation; South Africa; melanocortin 4 receptor; obesity