This study described single nucleotide polymorphisms (SNPs) in hydrochlorothiazide-associated genes and further assessed their correlation with blood pressure control among South African adults living with hypertension. A total of 291 participants belonging to the Nguni tribes of South Africa on treatment for hypertension were recruited. Nineteen SNPs in hydrochlorothiazide pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as blood pressure ≥140/90 mmHg. The association between genotypes, alleles and blood pressure response to treatment was determined by conducting multivariate logistic regression model analysis. The majority of the study participants were female (73.19%), Xhosa (54.98%) and had blood pressure ≥140/90 mmHg (68.73%). Seventeen SNPs were observed among the Xhosa tribe, and two (rs2070744 and rs7297610) were detected among Swati and Zulu participants. Furthermore, alleles T of rs2107614 (AOR = 6.69; 95%CI 1.42-31.55; p = 0.016) and C of rs2776546 (AOR = 3.78; 95%CI 1.04-13.74; p = 0.043) were independently associated with uncontrolled hypertension, whilst rs2070744 TC (AOR = 38.76; 95%CI 5.54-270.76; p = 0.00023), CC (AOR = 10.44; 95%CI 2.16-50.29; p = 0.003) and allele T of rs7297610 (AOR = 1.86; 95%CI 1.09-3.14; p = 0.023) were significantly associated with uncontrolled hypertension among Zulu and Swati participants. We confirmed the presence of SNPs associated with hydrochlorothiazide, some of which were significantly associated with uncontrolled hypertension in the study sample. Findings open doors for further studies on personalized therapy for hypertension in the country.
Keywords: South Africa; hydrochlorothiazide; pharmacogenomics; single nucleotide polymorphisms; uncontrolled hypertension.