Masilela Charity, Pearce Brendon, Ongole Joven Jebio, Adeniyi Oladele Vincent, Benjeddou Mongi
Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa.
Center for Teaching and Learning, Department of Family Medicine, Piet Retief Hospital, Mkhondo 2380, South Africa.
J Pers Med. 2020 Dec 9;10(4):267. doi: 10.3390/jpm10040267.
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; = 0.016) and C of rs2776546 (AOR = 3.78; 95%CI 1.04-13.74; = 0.043) were independently associated with uncontrolled hypertension, whilst rs2070744 TC (AOR = 38.76; 95%CI 5.54-270.76; = 0.00023), CC (AOR = 10.44; 95%CI 2.16-50.29; = 0.003) and allele T of rs7297610 (AOR = 1.86; 95%CI 1.09-3.14; = 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.
本研究描述了氢氯噻嗪相关基因中的单核苷酸多态性（SNP），并进一步评估了它们与南非成年高血压患者血压控制之间的相关性。共招募了291名接受高血压治疗的南非恩古尼部落参与者。选择了氢氯噻嗪药物代谢基因中的19个SNP，并使用MassArray进行基因分型。未控制的高血压定义为血压≥140/90 mmHg。通过进行多变量逻辑回归模型分析，确定基因型、等位基因与治疗后血压反应之间的关联。大多数研究参与者为女性（73.19%），科萨族（54.98%），且血压≥140/90 mmHg（68.73%）。在科萨族中观察到17个SNP，在斯瓦蒂族和祖鲁族参与者中检测到两个（rs2070744和rs7297610）。此外，rs2107614的等位基因T（比值比=6.69；95%置信区间1.42 - 31.55；P=0.016）和rs2776546的等位基因C（比值比=3.78；95%置信区间1.04 - 13.74；P=0.043）与未控制的高血压独立相关，而rs2070744的TC（比值比=38.76；95%置信区间5.54 - 270.76；P=0.00023）、CC（比值比=10.44；95%置信区间2.16 - 50.29；P=0.003）以及rs7297610的等位基因T（比值比=1.86；95%置信区间1.09 - 3.14；P=0.023）在祖鲁族和斯瓦蒂族参与者中与未控制的高血压显著相关。我们证实了与氢氯噻嗪相关的SNP的存在，其中一些在研究样本中与未控制的高血压显著相关。这些发现为该国高血压个性化治疗的进一步研究打开了大门。
