Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R.C; Institute of Clinical Pharmacology, Central South University, Changsha, P.R.C; Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R.C.
Second uropoiesis surgical department in Han Dan Central Hospital, Handan, P.R.C.
PLoS One. 2015 Apr 7;10(4):e0121483. doi: 10.1371/journal.pone.0121483. eCollection 2015.
Regulators of G-protein signaling protein 2 (RGS2) play an irreplaceable role in the control of normal blood pressure (BP). One RGS2 (-391, C>G) genetic variation markedly changes its mRNA expression levels. This study explored the relationship between this genetic variation and the responses to antihypertensive drugs in Chinese patients with essential hypertension.
Genetic variations of RGS2 were successfully identified in 367 specimens using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. All patients were treated with conventional doses of antihypertensives after a 2-week run-in period and followed-up according to our protocol. A general linear model multivariate analysis of variance (ANOVA) was used for the data analysis.
A significant difference in the mean systolic BP change was observed between RGS2 (-391, C>G) CC/CG (n = 82) and GG (n = 38) genotype carriers (-13.6 vs. -19.9 mmHg, P = 0.043) who were treated with candesartan, irbesartan or imidapril at the end of 6 weeks. In addition, the patients' BP responses to α,β-adrenergic receptor blockers exhibited an age-specific association with the RGS2 (-391, C>G) genetic variation at the end of 4 weeks.
The RGS2 (-391, C>G) genetic polymorphism may serve as a biomarker to predict a patient's response to antihypertensive drug therapy, but future studies need to confirm this.
G 蛋白信号调节蛋白 2(RGS2)在控制正常血压(BP)方面起着不可替代的作用。一种 RGS2(-391,C>G)遗传变异显著改变了其 mRNA 表达水平。本研究探讨了这种遗传变异与中国原发性高血压患者对降压药物反应之间的关系。
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析成功鉴定了 367 例标本中的 RGS2 遗传变异。所有患者在 2 周的导入期后接受常规剂量的降压治疗,并根据我们的方案进行随访。采用多元方差分析(ANOVA)对数据进行分析。
在接受坎地沙坦、厄贝沙坦或咪达普利治疗 6 周结束时,RGS2(-391,C>G)CC/CG(n=82)和 GG(n=38)基因型携带者的平均收缩压变化存在显著差异(-13.6 对-19.9mmHg,P=0.043)。此外,患者的血压对α、β肾上腺素能受体阻滞剂的反应在 4 周结束时与 RGS2(-391,C>G)遗传变异呈年龄特异性相关。
RGS2(-391,C>G)遗传多态性可能作为预测患者对降压药物治疗反应的生物标志物,但需要进一步的研究来证实这一点。