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细胞色素P450 2C9*3与血管紧张素II受体1(1166A>C)基因多态性与厄贝沙坦降压效果的关联

Association of Cytochrome P450 2C9*3 and Angiotensin II Receptor 1 (1166A>C) Gene Polymorphisms With the Antihypertensive Effect of Irbesartan.

作者信息

Dong Hui, Wang Feng-Zhen, Shi Kun, Zhang Xue-Shan, Lv Dong-Mei

机构信息

Department of Clinical Pharmacy, First Clinical College of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

出版信息

Am J Hypertens. 2021 Feb 18;34(1):121. doi: 10.1093/ajh/hpaa134.

DOI:10.1093/ajh/hpaa134
PMID:33599747
Abstract

BACKGROUND

To analyze whether the cytochrome P450 enzyme 2C93 (CYP2C93) and angiotensin II receptor 1 (AGTR1) (1166A>C) gene polymorphisms are associated with the risk of essential hypertension (EH) and the antihypertensive effect of irbesartan.

METHODS

A total of 2,057 EH patients and 286 healthy controls were enrolled for genotyping in which 598 EH patients were given irbesartan 150 mg/day for 4 weeks. Blood pressure of all subjects were determined before and at the end of 4-week treatment.

RESULTS

There was no significant difference in genotype frequencies of CYP2C93 and AGTR1 (1166A>C) between EH and control groups. Subjects with 13/33 genotypes of the CYP2C93 gene had larger systolic and diastolic blood pressure reductions (34.9 ± 15.5 vs. 29.3 ± 10.2 mm Hg and 22.8 ± 9.0 vs. 19.6 ± 8.5 mm Hg, respectively) compared with the 11 genotype. For AGTR1 (1166A>C) polymorphisms, although there was no significant difference among AC, CC, and AA genotypes, male subjects with AC/CC genotypes had larger systolic and diastolic blood pressure reductions (32.3 ± 1.3 vs. 29.3 ± 0.5 mm Hg and 21.6 ± 0.8 vs. 19.4 ± 0.1 mm Hg, respectively, P < 0.05) in response to irbesartan treatment compared with the AA genotype.

CONCLUSIONS

Polymorphisms of CYP2C9*3 and AGTR1 (1166A>C) are not significantly different between EH and healthy controls. Male subjects with AC and CC genotypes of AGTR1 (1166A>C) show better antihypertensive effect of irbesartan than the AA genotype.

摘要

背景

分析细胞色素P450酶2C93(CYP2C93)和血管紧张素II受体1(AGTR1)(1166A>C)基因多态性与原发性高血压(EH)风险及厄贝沙坦降压效果的相关性。

方法

共纳入2057例EH患者和286例健康对照进行基因分型,其中598例EH患者给予厄贝沙坦150mg/天,治疗4周。测定所有受试者治疗前及治疗4周后的血压。

结果

EH组与对照组之间CYP2C93和AGTR1(1166A>C)的基因型频率无显著差异。与11基因型相比,CYP2C93基因13/33基因型的受试者收缩压和舒张压降低幅度更大(分别为34.9±15.5 vs. 29.3±10.2mmHg和22.8±9.0 vs. 19.6±8.5mmHg)。对于AGTR1(1166A>C)多态性,虽然AC、CC和AA基因型之间无显著差异,但与AA基因型相比,AC/CC基因型的男性受试者在接受厄贝沙坦治疗后收缩压和舒张压降低幅度更大(分别为32.3±1.3 vs. 29.3±0.5mmHg和21.6±0.8 vs. 19.4±0.1mmHg,P<0.05)。

结论

EH患者与健康对照者之间CYP2C9*3和AGTR1(1166A>C)的多态性无显著差异。AGTR1(1166A>C)基因AC和CC基因型的男性受试者使用厄贝沙坦的降压效果优于AA基因型。

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