Association of Cocaine- and Amphetamine-Related Transcript, Leptin and Leptin Receptor Gene Polymorphisms with Anthropometric Obesity Phenotype Indicators in South African Learners

Abstract

Background/Aims: Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Methods: Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. Results: The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys¹⁰⁹Arg G allele was associated with an average reduction of 2.36 kg/m² in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Conclusion: Our findings suggest that c.517A→G and Lys¹⁰⁹Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group.

Genetic association studies of obesity in Africa: a systematic review

“…Adjustment for confounders was not consistent across studies, with 15 studies not providing information on the degree of adjustment or variables accounted for. Among 10 studies that included multiethnic populations, seven provided information on the approach used to adjust for population stratification either by conducting the analysis separately for each ethnic group or accounting for ethnicity , using a transmission disequilibrium test , first principal component analysis from a set of 142 ancestry‐informative SNPs or a set of 18 ancestral informative markers to determine a population substructure on the STRUCTURE V.2.3.3 software, Pritchard Lab, Stanford University, Stanford, California, United States of America .…”

Social and Psychological Predictors of Body Mass Index among South Africans 15 Years and Older: SANHANES-1

“…Unhealthy weight (underweight and obesity) is rife [1,2,3,4], heterogeneous, and uneven across population groups in South Africa [5,6,7]. This is thought to be influenced by a myriad of factors that include socio-demography, psychology, environment, behaviors and genetics [8,9,10,11,12,13,14,15,16]. For the last two decades, as a result of urbanization and globalization, South Africa has been contending with a nutrition transition which has in turn resulted in an epidemiological transition [1,2,3,4].…”

“…It is important to remember that while genetics are a strong risk factor for obesity in South Africa [13,14,15], evidence has also highlighted an additional interplay between genetics and other determinants such as sociodemography, especially the social position (also known as social standing) [23], environment, and behaviors [16,17,24,25]. In fact, international evidence has suggested contradictory associations (i.e., both positive and negative) between social position and BMI [7,26,27,28].…”