Department of Biomedical Science, Genetic Research Group, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM Serdang Selangor, Malaysia.
Malaysian Research Institute on Ageing, University Putra Malaysia, UPM Serdang Selangor, Malaysia.
Arch Med Res. 2017 Jan;48(1):88-95. doi: 10.1016/j.arcmed.2017.03.003.
Essential Hypertension (EH) is a common disorder associated with increased cardiovascular morbidity and mortality in Malaysia. To investigate how genetic polymorphisms of the renin-angiotensin-aldosterone system (RAS) influence EH control with angiotensin-converting enzyme inhibitor drugs (ACEI).
A case-control, cross-sectional population-based nested study (n = 142) included hypertensive subjects treated with ACEI drugs, either lisinopril or enalapril (20 mg, once daily) as monotherapy for 24 weeks. In total seven possible polymorphisms of RAS genes were genotyped. The association between those polymorphisms and the changes in blood pressure were observed in the 24 week treatment.
Statistically significant associations of I, G, T, M and G alleles of ACE (I/D, G2350A), AGT (M235T, T175M and G-6A) respectively were observed in essential hypertensive subjects. The decrease in systolic blood pressure and diastolic blood pressure after 24 weeks of treatment of the patients carrying II, GG, and TT genotypes were greater than the groups carrying DD, AA, MM, MM and GG of I/D, G2350A, M235T, T174M and G-6A genotypes respectively. In contrast, No significant difference was observed between renin gene polymorphisms (Bg/I and MboI) and hypertensives.
Although this study shows a possible association of polymorphisms of RAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.
原发性高血压(EH)是一种常见疾病,与马来西亚心血管发病率和死亡率的增加有关。本研究旨在探讨肾素-血管紧张素-醛固酮系统(RAS)的遗传多态性如何影响血管紧张素转换酶抑制剂(ACEI)药物治疗的原发性高血压控制情况。
采用病例对照、横断面、基于人群的嵌套研究(n=142),纳入接受 ACEI 药物(依那普利或赖诺普利,20mg,每日一次)单药治疗 24 周的高血压患者。共对 RAS 基因的 7 种可能的多态性进行了基因分型。观察了这些多态性与 24 周治疗期间血压变化之间的关系。
在原发性高血压患者中,ACE(I/D、G2350A)、AGT(M235T、T175M 和 G-6A)的 I、G、T、M 和 G 等位基因存在统计学显著相关性。与携带 DD、AA、MM、MM 和 GG 基因型的患者相比,携带 II、GG 和 TT 基因型的患者在接受 24 周治疗后,收缩压和舒张压下降幅度更大。相比之下,肾素基因多态性(Bg/I 和 MboI)与高血压患者之间无显著差异。
尽管本研究显示 RAS 基因多态性与 ACEI 治疗患者 HT 控制不佳的风险之间可能存在关联,并表明该系统所有成分在调节 HT 中的重要性,但仍需在其他数据源中进行复制。