Possible association between genetic polymorphisms of the adrenergic receptor genes and obesity and hypertension in South African female volunteers

Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.

Introduction: Across the world the incidence of the metabolic syndrome increases annually at an alarming rate. Two conditions associated with this are obesity and hypertension (high blood pressure). Both have negative health and lifestyle consequences, numerous studies on adrenergic receptor (AR) gene polymorphisms in various population groups have proved, although not exclusively, that these polymorphisms may be positively associated with susceptibility to and progression of obesity and hypertension. The AR encoding genes are attractive targets for such studies because the ARs, as part of the sympathetic nervous system, perform important functions like vasoconstriction, vasodilation, lipolysis and influence the heart's contraction. These functions accentuate the possible role of AR gene polymorphisms in the onset or progression of obesity and hypertension. Obesity is a health concern especially among black South African women. The prevalence of obesity (BMI > 30 kg/m2) in the North-West province of South Africa is high: 28.6%. The POWIRS (Profile of Obese Women with the Insulin Resistance syndrome) study was conducted in 2003 on 102 black South African female volunteers to search for possible associations of the p2-AR Gln27Glu and p3-AR Trp64Arg polymorphisms with parameters of the carbohydrate and lipid metabolism, the index of insulin resistance (HOMA-IR), body mass index (BMI) and body fat % (Schutte et al., 2005). To our knowledge, this was the first study of its kind in South Africa and which led to this study and dissertation. Objectives: The objectives of this study were to: • Determine the incidence of the following polymorphisms in (a) 102 black South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; (b) 115 white South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; Gln27Glu; B3-AR: Trp64Arg; • identify possible diplotypes and haplotypes in the study groups; • take relevant physiological parameters (measured in the POWIRS studies) into account in the search for possible associations of these polymorphisms, diplotypes and haplotypes with obesity and high blood pressure as characteristics of the metabolic syndrome; • compare the black and the white study groups with regards to the above mentioned objectives. Methods: DNA was isolated from blood spots on Guthrie cards (collected during the POWIRS studies) and the respective AR gene regions amplified by polymerase chain reaction (PCR). After restriction enzyme digestion, the DIVA fragments were separated by agarose gel electrophoresis. Genotypic findings were examined along with measured physiological parameters (measured during the POWIRS studies) and statistically processed. Area under the curve (AUC) analysis was performed on parameters measured during the oral glucose tolerance test. Diplotype and haplotype analyses were also performed on both subject groups. Results: The minor allele frequencies for both groups were calculated and compared to that reported in other published studies. For the black group, the minor allele frequencies were: 84% (B1-AR Ser49Gly), 16% (B2-AR Gln27Glu), 49% (B2-AR Arg16Gly) and 28% (B3-AR Trp64Arg) and for the white group: 94%, 46%, 50% and 7% respectively. The AUC differed in almost every instance of comparison, but was within normal ranges. Only a few significant differences were identified when the measured physiological parameters were compared between the genotypes, diplotypes and haplotypes in each group, most of which were found to be within normal ranges. When the two groups of test subjects were compared, only minimal differences were observed, most of which were still found to be well within normal ranges. Conclusions: Although no associations were identified between the separate investigated AR gene polymorphisms, diplotypes or haplotypes and obesity and hypertension or high blood pressure, indications are present that they may act as contributors to risk factors for the onset and progression of these characteristics of the metabolic syndrome.

Masters