Renin-angiotensin-aldosterone system gene polymorphisms and antihypertensive response to irbesartan in Chinese hypertensives.
The aim of this study was to determine whether specific single nucleotide polymorphisms (SNPs) and their reconstructed haplotypes in renin-angiotensin-aldosterone system (RAAS) genes were associated with antihypertensive reduction to irbesartan treatment. Thousand one forty-two hypertensives were recruited and received 150 mg irbesartan daily for 4 weeks. Blood pressures (BPs) and blood samples, at postdose on the 28th day, were measured. Predose BPs and plasma irbesartan concentrations were also measured. Involved SNPs in RAAS pathway genes were genotyped. Genotype (-344 TC) in the CYP11B2 had a significantly greater systolic blood pressure (SBP) reduction versus the TT genotype (p = 0.001). Subjects with the 174MM genotype of the angiotensinogen (AGT) gene had a significantly greater average SBP reduction (p = 0.025). The C-344T and T1016C polymorphisms in the CYP11B2 gene were both significantly associated with diastolic blood pressure (DBP) reduction (p = 0.026 or p = 0.003). Overall, the three loci-constructed haplotypes of the CYP11B2 gene were associated with DBP reduction (p = 0.008). Haplo-GLM analyses demonstrated that subjects with haplotype CTA had a significantly greater SBP and DBP reductions (p < 0.001 or p = 0.020), whereas subjects with haplotype TAA had a significantly lower SBP and DBP reductions (p < 0.001). Our findings suggested that SNPs and their reconstructed haplotypes in RAAS genes might be involved in the regulation of BP-lowering response to irbesartan in Chinese hypertensives.
Liu
H
H
School of Life Science, University of Science and Technology of China, Hefei, Anhui, China. xipingxu@uic.edu
Zhang
S
S
Jiang
S
S
Mao
G
G
Hong
X
X
Yu
Y
Y
Zhang
Y
Y
Tang
G
G
Xing
H
H
Xu
X
X
D000808:Angiotensinogen / Q000235:genetics; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D044466:Asian People; D001713:Biphenyl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002681:China; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System / Q000235:genetics*; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000808:Angiotensinogen; D000077405:Irbesartan