首页> 外文期刊>Journal of hypertension >Interactive effect of angiotensin II type 1 receptor (AGT1R) polymorphisms and plasma irbesartan concentration on antihypertensive therapeutic responses to irbesartan.
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Interactive effect of angiotensin II type 1 receptor (AGT1R) polymorphisms and plasma irbesartan concentration on antihypertensive therapeutic responses to irbesartan.

机译:血管紧张素II 1型受体(AGT1R)多态性和血浆厄贝沙坦浓度对对厄贝沙坦的降压治疗反应的相互作用。

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摘要

BACKGROUND: 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. METHODS: 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. RESULTS: When stratified by genotypes, patients carrying allele C of single-neucleotide polymorphism (SNP) rs5186 showed positive association between irbesartan concentration and BP response [SBP: beta +/- SE=6.1 +/- 2.3 with false discovery rate (FDR) P=0.029; DBP: beta +/- 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. CONCLUSION: Our data suggest that AGT1R gene polymorphisms and plasma concentration of irbesartan can act interactively to modulate individual response to antihypertensive therapy using irbesartan.
机译:背景:研究血浆厄贝沙坦浓度和血管紧张素II 1型受体(AGT1R)基因多态性对厄贝沙坦治疗对血压(BP)反应的相互作用。方法:本研究包括1049名中国高血压患者,他们每天口服150 mg厄贝沙坦治疗4周。在服药前和治疗第28天测量BP,并测量血浆厄贝沙坦的谷浓度(在治疗第28天)。对四个AGT1R基因多态性(rs2640539,rs1492097,rs388915,rs5186)进行基因分型。使用多个线性回归模型评估血浆厄贝沙坦浓度和基因多态性对BP反应的相互作用,并调整协变量。结果:按基因型分层时,携带单核苷酸多态性(SNP)rs5186等位基因C的患者显示厄贝沙坦浓度与BP反应呈正相关[SBP:β+/- SE = 6.1 +/- 2.3与假发现率(FDR) P = 0.029; DBP:β+/- SE = 2.7 +/- 1.0,FDR P = 0.029],但这在AA基因型患者中未见。血浆厄贝沙坦浓度和SNP rs5186在SBP反应(相互作用P = 0.0335)和DBP反应(相互作用P = 0.0190)之间存在显着相互作用。血浆厄贝沙坦浓度与hap3,hap5和hap6(由四个基因型SNP构成)之间在SBP应答(FDR P <0.001)上,但在DBP应答上也没有显着的相互作用。结论:我们的数据表明,厄贝沙坦的AGT1R基因多态性和血浆浓度可以相互作用,调节个体对使用厄贝沙坦的降压治疗的反应。

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