School of Life Sciences, Anhui University, 3 Feixi Road, P.O. Box 41, Hefei 230039, China.
J Hypertens. 2011 May;29(5):890-5. doi: 10.1097/HJH.0b013e32834494f6.
To investigate the interactive effect of plasma irbesartan concentration and angiotensin II type 1 receptor (AGT1R) gene polymorphisms on blood pressure (BP) response to irbesartan treatment.
This study included 1049 Chinese hypertensive patients who were treated with daily oral 150 mg irbesartan for 4 weeks. BP at predose and 28th day of treatment and trough plasma irbesartan concentration (on 28th day of treatment) were measured. Four AGT1R gene polymorphisms (rs2640539, rs1492097, rs388915, rs5186) were genotyped. Multiple linear regression models were used to assess interactive effect of plasma irbesartan concentration and gene polymorphisms on BP response, with adjustment for covariates.
When stratified by genotypes, patients carrying allele C of single-neucleotide polymorphism (SNP) rs5186 showed positive association between irbesartan concentration and BP response [SBP: β ± SE=6.1 ± 2.3 with false discovery rate (FDR) P=0.029; DBP: β ± SE=2.7 ± 1.0 with FDR P=0.029], but this was not seen in patients with AA genotype. There was a significant interaction between plasma irbesartan concentration and SNP rs5186 on SBP response (interaction P=0.0335) and DBP response (interaction P=0.0190). There also were significant interactions between plasma irbesartan concentration and hap3, hap5 and hap6 (constructed by four genotyped SNPs) on SBP response (FDR P<0.001), but not on DBP response.
Our data suggest that AGT1R gene polymorphisms and plasma concentration of irbesartan can act interactively to modulate individual response to antihypertensive therapy using irbesartan.
为了研究血管紧张素Ⅱ 1 型受体（AGT1R）基因多态性与血浆氯沙坦浓度对氯沙坦降压疗效的交互作用。
本研究纳入了 1049 例中国高血压患者，他们每天口服 150mg 氯沙坦治疗 4 周。在治疗前和第 28 天测量血压，在第 28 天测量氯沙坦的谷浓度。对 4 个 AGT1R 基因多态性（rs2640539、rs1492097、rs388915、rs5186）进行基因分型。采用多元线性回归模型，在调整协变量后，评估氯沙坦浓度和基因多态性对血压反应的交互作用。
按单核苷酸多态性（SNP）rs5186 基因型分层，携带 SNP rs5186 等位基因 C 的患者，氯沙坦浓度与血压反应呈正相关[收缩压：β ± SE=6.1 ± 2.3，经错误发现率（FDR）校正 P=0.029；舒张压：β ± SE=2.7 ± 1.0，FDR P=0.029]，但 AA 基因型患者则无此现象。氯沙坦浓度与 SNP rs5186 对收缩压反应的交互作用有统计学意义（交互作用 P=0.0335），对舒张压反应的交互作用也有统计学意义（交互作用 P=0.0190）。氯沙坦浓度与构建的 haplotype3、haplotype5 和 haplotype6（由 4 个基因分型 SNP 组成）对收缩压反应的交互作用也有统计学意义（经 FDR 校正 P<0.001），但对舒张压反应则无统计学意义。
本研究数据表明，AGT1R 基因多态性和氯沙坦的血浆浓度可以相互作用，调节个体对氯沙坦降压治疗的反应。
