CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt
CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt
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DOI：
10.1161/hypertensionaha.106.084236
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发表时间：
2007-05-01
期刊：
影响因子：
8.3
通讯作者：
Burnier, Michel
中科院分区：
文献类型：
--
作者：
Eap, Chin B.;Bochud, Murielle;Burnier, Michel
已知由多药耐药1（ABCB 1）基因编码的渗透性糖蛋白外排转运蛋白和由CYP 3A 4/5基因编码的细胞色素P450 3A 4/5在许多药物的转运和代谢中相互作用。最近的数据表明，CYP 3A 5基因型影响血压，渗透性糖蛋白活性可能影响肾素-血管紧张素系统的活性。因此，这两个基因可能有助于人类的血压调节。我们分析了72个东非血统家庭（373人; 55%为女性;平均年龄：46岁）ABCB 1和CYP 3A 5基因变异与动态血压、血浆肾素活性、血浆醛固酮、内源性锂清除率和治疗后血压反应的相关性。ABCB 1和CYP 3A 5基因与尿钠排泄相互作用，影响动态血压（白天收缩压：P = 0.05;夜间收缩压和舒张压：P < 0.01），提示基因-基因-环境相互作用。这些基因的联合作用也与近端小管后钠重吸收、血浆肾素活性、血浆醛固酮以及对血管紧张素转换酶抑制剂赖诺普利的血压反应改变有关（P < 0.05）。这是首次报道ABCB 1基因与人类血压的相关性，并证明编码代谢和转运药物和内源性底物的蛋白质的基因有助于血压调节。
The permeability - glycoprotein efflux-transporter encoded by the multidrug resistance 1 (ABCB1) gene and the cytochromes P450 3A4/5 encoded by the CYP3A4/5 genes are known to interact in the transport and metabolism of many drugs. Recent data have shown that the CYP3A5 genotypes influence blood pressure and that permeability - glycoprotein activity might influence the activity of the renin - angiotensin system. Hence, these 2 genes may contribute to blood pressure regulation in humans. We analyzed the association of variants of the ABCB1 and CYP3A5 genes with ambulatory blood pressure, plasma renin activity, plasma aldosterone, endogenous lithium clearance, and blood pressure response to treatment in 72 families ( 373 individuals; 55% women; mean age: 46 years) of East African descent. The ABCB1 and CYP3A5 genes interact with urinary sodium excretion in their effect on ambulatory blood pressure ( daytime systolic: P = 0.05; nighttime systolic and diastolic: P < 0.01), suggesting a gene - gene - environment interaction. The combined action of these genes is also associated with postproximal tubular sodium reabsorption, plasma renin activity, plasma aldosterone, and with an altered blood pressure response to the angiotensin-converting enzyme inhibitor lisinopril ( P < 0.05). This is the first reported association of the ABCB1 gene with blood pressure in humans and demonstration that genes encoding for proteins metabolizing and transporting drugs and endogenous substrates contribute to blood pressure regulation.