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.

Interaction between Metabolic Genetic Risk Score and Dietary Fatty Acid Intake on Central Obesity in a Ghanaian Population

“…We found that none of the metabolic GRSs were significantly associated with obesity-related traits in the Ghanaian population, which contradicts the findings of the previous GRS-related studies in European and African populations [15,[25][26][27][28][29][30]32,33]. Efforts to replicate previously reported genetic associations of individual SNPs with obesity measures in non-African populations have shown limited success among Africans [23,31,51,52], which is also in line with the findings from the present study. Several factors are likely to be involved in such discrepancies between our findings and genetic association studies in Europeans.…”

<p>Identification of the <em>MC4R</em> start lost mutation in a morbidly obese Brazilian patient</p>

“…Epidemiologic data have estimated that 0.05% individuals have variations in MC4R in general population 16,17. Furthermore, the prevalence of MC4R variants in adult with obesity is 0.2% and ~5%–6% in patients with severe early-onset obesity 18,19.…”

Clinical and Functional Characterization of Melanocortin 4 Receptor genetic variants in African American and/or Hispanic children with severe early onset obesity.

“…While the obesity epidemic has disproportionately affected non-Hispanic African-American and Hispanic youth in the United States (6), little is known about the prevalence of MC4R mutations in children of these ethnicities. In a recently published study of 25 unrelated Afro-Caribbean children with obesity from the Guadeloupe Island, one 11.8 year-old boy had a p. Ile301Thr mutation in MC4R (7), while in a study of South African adults of mixed ancestry that included 63% Black Africans (n = 187), 2.6% harbored a rare MC4R variant (8). These studies provide early clues on the expected prevalence of MC4R variants in children of non-European ancestry.…”