CYP3A5 genotype is associated with diagnosis of hypertension in elderly patients: data from the DEBATE Study.

Kari T Kivistö, Mikko Niemi, Elke Schaeffeler, Kaisu Pitkälä, Reijo Tilvis, Martin F Fromm, Matthias Schwab, Florian Lang, Michel Eichelbaum, Timo Strandberg
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引用次数: 43

Abstract

Objective: The aim of this study was to address the presently controversial question of whether cytochrome P450 (CYP) 3A5 polymorphism is associated with hypertension.

Method: We studied 373 elderly (age > or =75 years) Finnish (Caucasian) patients from the ongoing DEBATE (Drugs and Evidence Based Medicine in the Elderly) trial. The patients were classified into those with a history of hypertension (n = 229) and those without a history of hypertension (n = 144) on the basis of a detailed questionnaire on each patient's medical history and an interview. The patients were genotyped for the CYP3A5 6986A/G single nucleotide polymorphism (SNP) [CYP3A5*1/*3 alleles].

Results: The proportion of individuals with the CYP3A5*1/*3 genotype, i.e. CYP3A5 expressors, was significantly higher among patients with a diagnosis of hypertension than among patients without (18.3% vs 9.0%, p = 0.016). The corresponding odds ratio was 2.26 (95% CI 1.17, 4.38). The allele and genotype frequencies for the two control SNPs, ABCB1 (MDR1) 3435C/T and SLCO1B1 521T/C, did not differ between the two groups.

Conclusion: This work lends support to the theory that the polymorphic CYP3A5 enzyme may be involved in regulation of blood pressure. The possible role of CYP3A5 as a genetic contributor to hypertension susceptibility warrants further study.

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CYP3A5基因型与老年高血压患者的诊断相关:来自DEBATE研究的数据
目的:本研究的目的是解决目前有争议的问题,即细胞色素P450 (CYP) 3A5多态性是否与高血压有关。方法:我们研究了373名老年(年龄>或=75岁)芬兰(高加索)患者,他们来自正在进行的DEBATE(老年药物和循证医学)试验。通过对患者进行详细的病史问卷调查和访谈,将患者分为有高血压史(229例)和无高血压史(144例)。对患者进行CYP3A5 6986A/G单核苷酸多态性(SNP) [CYP3A5*1/*3等位基因]基因分型。结果:诊断为高血压的患者中CYP3A5*1/*3基因型(即CYP3A5表达物)个体比例显著高于未诊断为高血压的患者(18.3% vs 9.0%, p = 0.016)。相应的优势比为2.26 (95% CI 1.17, 4.38)。ABCB1 (MDR1) 3435C/T和SLCO1B1 521T/C两个对照snp的等位基因频率和基因型频率在两组间无差异。结论:本研究支持CYP3A5酶多态性可能参与血压调节的理论。CYP3A5作为高血压易感性遗传因素的可能作用值得进一步研究。
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