Relation of renin-angiotensin system gene polymorphisms and expressions with the efficacy of antihypertensive drugs.
OBJECTIVE: To investigate the relation of renin-angiotensin system (RA3) gene polymorphisms and expressions with the clinical efficacy of antihypertensive drugs. METHODS: This randomized, single-blind study consisted of 90 patients with essential hypertension, who were divided into losartan, lisinopril and nisodipine groups with corresponding medications as indicated. The genotypes of angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T polymorphism and expressions of ACE and AT1 receptor genes were examined individually. RESULTS: The basal level of mRNA expression of AT1 receptor was lower in patients with MM genotype of AGT gene than those in patients with MT 1 and TT genotypes, but between the latter two, no significant differences were found. The three antihypertensive drugs, when significantly lowering the blood pressure, reduced AT1 receptor mRNA expression concurrently. Losartan and lisinopril both decreased ACE mRNA expression levels that were positively correlated with the difference of the diastolic blood pressure whereas nisodipine elevated ACE mRNA expression, showing inverse correlation to the difference of thediastolic blood pressure. CONCLUSION: For patients with hypertension who have elevated basal levels of AT1 mRNA expression and AGT T allele or who retain high basal expression levels of ACE mRNA AT1 antagonists and ACE inhibitors that execute their action through RAS are preferentially selected, and in cases of low basal levels of ACE mRNA calcium antagonists are preferred.
Wei
Xiang-Long
XL
Department of Cardiology, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China.
Zhao
Guang-Sheng
GS
Wang
Gu-Liang
GL
Li
Di-Yuan
DY
Guo
Ji-Zhen
JZ