Polonikov Alexey V, Ivanov Vladimir P, Solodilova Maria A, Khoroshaya Irina V, Kozhuhov Mikhail A, Ivakin Vladimir E, Katargina Ludmila N, Kolesnikova Ol'ga E
Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia.
Dis Markers. 2008;24(2):119-26. doi: 10.1155/2008/626430.
The present study was designed to test whether common polymorphism G-50T within the promoter of human CYP2J2 gene is associated with increased risk of essential hypertension in a Russian population. We studied 576 unrelated subjects, including 295 patients with hypertension and 281 healthy subjects. Genotyping for polymorphism G-50T of the CYP2J2 gene was performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The frequency of a -50T variant allele of CYP2J2 gene was significantly higher in patients with hypertension versus healthy controls (OR 4.03 95%CI 1.80-9.04 p=0.0004). The association of a -50GT genotype with hypertension remained significant after adjustment for age, gender and family history of hypertension by multivariate logistic regression (OR 4.78 95%CI 1.87-12.27 p=0.001). It has been found that OR for -50GT genotype x gender interaction (OR 4.48 95%CI 1.93-10.39 p=0.00048) was slightly higher than OR for -50GT genotype (OR 4.43 95%CI 1.91-10.29 p=0.00052), suggesting a weak effect of gender on the risk of hypertension in the heterozygous carriers of -50GT genotype. A family history of hypertension has no effect on the association between a -50GT genotype and hypertension. In present study we demonstrate for the first time that a CYP2J2*7 allele of the CYP2J2 gene is clearly associated with an increased risk of essential hypertension. Furthermore, this study highlights the importance of P-450 epoxygenase pathway of arachidonic acid metabolism in the pathogenesis of hypertensive disease.
本研究旨在检测人类CYP2J2基因启动子区域常见的G-50T多态性是否与俄罗斯人群原发性高血压风险增加相关。我们研究了576名无亲缘关系的受试者,其中包括295例高血压患者和281名健康受试者。采用聚合酶链反应和限制性片段长度多态性技术对CYP2J2基因的G-50T多态性进行基因分型。与健康对照组相比,高血压患者中CYP2J2基因-50T变异等位基因的频率显著更高(比值比4.03,95%置信区间1.80 - 9.04,p = 0.0004)。经多因素逻辑回归对年龄、性别和高血压家族史进行校正后,-50GT基因型与高血压之间的关联仍然显著(比值比4.78,95%置信区间1.87 - 12.27,p = 0.001)。已发现-50GT基因型与性别的交互作用的比值比(比值比4.48,95%置信区间1.93 - 10.39,p = 0.00048)略高于-50GT基因型的比值比(比值比4.43,95%置信区间1.91 - 10.29,p = 0.00052),这表明性别对-50GT基因型杂合携带者的高血压风险有微弱影响。高血压家族史对-50GT基因型与高血压之间的关联没有影响。在本研究中,我们首次证明CYP2J2基因的CYP2J2*7等位基因与原发性高血压风险增加明显相关。此外,本研究强调了花生四烯酸代谢的P-450环氧酶途径在高血压疾病发病机制中的重要性。