Doctoral Degrees (Chemical Pathology)

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Browsing Doctoral Degrees (Chemical Pathology) by Subject "Dissertations -- Genetics"

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    Molecular investigation of genetic and environmental factors contributing to obesity in adolescent learners residing in the semi-urban/rural areas of the Western Cape Province, South Africa
    (Stellenbosch : Stellenbosch University, 2012-12) Yako, Yandiswa Yolanda; Erasmus, Rajiv T.; Matsha, Tandi; Janse van Rensburg, Susan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Chemical Pathology.
    ENGLISH ABSTRACT: Background/Aims: Obesity has increased rapidly in South African children and adolescents with significant variability observed among racial groups. Genes that regulate appetite have been studied in different populations worldwide, but their role in obesity among South African adolescents is unknown. The present study aimed at investigating the role of these genes, and their combined effect with physical activity in the development of obesity among South African adolescents. Methods: A total of 1564 South African school learners of Caucasian (n= 146), Mixed Ancestry (n= 872) and Black African (n= 537) ethnic groups were recruited for a research project that aimed to elucidate diabetes and the metabolic syndrome in children and adolescents attending schools in periurban areas of the Western Cape. The present case-control study included 227 obese-overweight (115 Black Africans and 112 Mixed Ancestry), and 204 normal weight (94 Black Africans and 110 Mixed Ancestry) adolescents learners. The learners were genotyped for nine polymorphisms (LEP: 19G>A, Lys36Arg, Val94Met; LEPR: Lys109Arg; Gln223Arg, Lys656Asn; CART: c.160-33G>A, c.499delA, and c.517A>G; GHRL: Leu72Met; and MC3R: Thr6Lys, Val81Ile) using allele-specific restriction enzyme analysis and automated sequencing. Genotype and haplotype associations with anthropometric variables such as body mass index (BMI), waist, hip, and mid-upper-arm circumferences (WC, HC, MUAC), and metabolic traits (fasting blood glucose, high density lipoproteincholesterol, total cholesterol), and blood pressure were further conducted. Furthermore, the type and frequency of physical activity was assessed by means of structured questionnaires; and its effect on obesity-related variables investigated in learners that were genotyped for the MC3R Thr6Lys and Val81Ile polymorphisms. Results: In a stepwise backward logistic regression analysis (containing age, gender, and LEP, LEPR, CART and GHRL polymorphisms), CART c.517A>G was independently significantly associated with obesity (OR= 5.98; 95%CI= 2.02, 21.27). CART c.517G carriers had higher MUAC (b coefficient= 1.88; 95%CI= 0.31, 3.44) while the LEPR 109Arg allele was significantly associated with decreased BMI (b coefficient = -2.36; 95%CI= -4.24, -0.47), WC (b coefficient = -5.66; 95%CI= -9.89, -1.44) and MUAC (b coefficient = -1.61; 95%CI= -3.00, -0.22); after adjusting for age, gender, and ethnicity. The haplotype containing the three LEP polymorphisms (A-A-A compared to the reference G-A-G haplotype) increased BMI (p= 0.0155), MUAC (p= 0.0146), and HC (p= 0.0128). The minor alleles of the MC3R polymorphisms decreased BMI, HC, WC, MUAC and TC; whilst only the Thr6Lys was associated with systolic and diastolic blood pressure (p= 0.0047 and 0.0027, respectively) in Mixed Ancestry learners. Doing house chores was associated with lower total cholesterol, independently and in the presence of the 81Ile allele (b coefficient = -0.355; 95%CI= 0.148, 0.561). Conclusion: To our knowledge, this is the first study that reports CART c.517A>G polymorphism as a risk factor for obesity in adolescents. Furthermore, the present study demonstrated that the MC3R polymorphisms had a positive effect on total cholesterol, which was further enhanced in physically active individuals. Similar to other studies, LEPR Lys109Arg and LEP polymorphisms were associated with variations in obesity-related variables among Black African and Mixed Ancestry South African learners.