Department of Biotechnology, University of the Western Cape, Bellville, South Africa.
Department of Family Medicine, Center for Teaching and Learning, Piet Retief Hospital, Mkhondo, South Africa.
Medicine (Baltimore). 2021 Nov 19;100(46):e27836. doi: 10.1097/MD.0000000000027836.
This study investigates the association of 5 single nucleotide polymorphisms (SNPs) in selected genes (ABO, VEGFA, BDKRB2, NOS3, and ADRB2) with blood pressure (BP) response to enalapril. The study further assessed genetic interactions that exist within these genes and their implications in enalapril treatment response among South African adults with hypertension.A total of 284 participants belonging to the Nguni tribe of South Africa on continuous treatment for hypertension were recruited. Five SNPs in enalapril pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as BP ≥140/90 mm Hg. The association between genotypes, alleles, and BP response to treatment was determined by fitting multivariate logistic regression model analysis, and genetic interactions between SNPs were assessed by multifactor dimensionality reduction.Majority of the study participants were female (75.00%), Xhosa (78.87%), and had uncontrolled hypertension (69.37%). All 5 SNPs were exclusively detected among Swati and Zulu participants. In the multivariate (adjusted) logistic model analysis, ADRB2 rs1042714 GC (adjusted odds ratio [AOR] = 2.31; 95% confidence interval [CI] 1.02-5.23; P = .044) and BDKRB2 rs1799722 CT (AOR = 2.74; 95% CI 1.19-6.28; P = .017) were independently associated with controlled hypertension in response to enalapril. While the C allele of VEGFA rs699947 (AOR = 0.37; 95% CI 0.15-0.94; P = .037) was significantly associated with uncontrolled hypertension. A significant interaction between rs699947, rs495828, and rs2070744 (cross-validation consistency = 10/10; P = .0005) in response to enalapril was observed.We confirmed the association of rs1042714 (ADRB2) and rs1799722 (BDKRB2) with controlled hypertension and established an interaction between rs699947 (VEGFA), rs495828 (ABO), and rs2070744 (NOS3) with BP response to enalapril. Our findings have provided substantial evidence for the use of SNPs as predictors for enalapril response among South Africans adults with hypertension.
这项研究调查了五个单核苷酸多态性（SNPs）在选定基因（ABO、VEGFA、BDKRB2、NOS3 和 ADRB2）中的关联，这些基因与依那普利的血压反应有关。该研究进一步评估了这些基因中存在的遗传相互作用及其对南非高血压成年人依那普利治疗反应的影响。
总共招募了 284 名属于南非 Nguni 部落的高血压连续治疗患者。选择了依那普利药代基因中的五个 SNPs，并使用 MassArray 进行了基因分型。未控制的高血压定义为 BP≥140/90mmHg。通过拟合多变量逻辑回归模型分析，确定了基因型、等位基因与治疗后血压反应之间的关系，并通过多因素降维法评估了 SNPs 之间的遗传相互作用。
研究参与者主要为女性（75.00%）、祖鲁人（78.87%）和未控制的高血压（69.37%）。所有 5 个 SNPs 仅在斯瓦提和祖鲁参与者中被检测到。在多变量（调整）逻辑回归模型分析中，ADRB2 rs1042714 GC（调整后的优势比[OR] = 2.31；95%置信区间[CI] 1.02-5.23；P=0.044）和 BDKRB2 rs1799722 CT（OR=2.74；95%CI 1.19-6.28；P=0.017）与依那普利治疗后的控制高血压独立相关。而 VEGFA rs699947 的 C 等位基因（OR=0.37；95%CI 0.15-0.94；P=0.037）与未控制的高血压显著相关。rs699947、rs495828 和 rs2070744 之间存在显著的相互作用（交叉验证一致性=10/10；P=0.0005），与依那普利的反应有关。
我们证实了 rs1042714（ADRB2）和 rs1799722（BDKRB2）与控制高血压有关，并建立了 rs699947（VEGFA）、rs495828（ABO）和 rs2070744（NOS3）与依那普利治疗后血压反应之间的相互作用。我们的研究结果为 SNPs 作为南非高血压成年人依那普利反应预测因子的应用提供了充分的证据。
