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Article type: Research Article
Authors: 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.
Affiliations: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia | Kursk Regional Clinical Hospital, Kursk, Russia | Kursk Emergency Medicine Hospital, Kursk, Russia
Note: [] Corresponding author: Alexey V. Polonikov, MD, PhD., Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Karl Marx Str. 3, 305041 Kursk, Russia. Tel./Fax: +7 4712 58 81 47; E-mail: polonikov@rambler.ru
Abstract: 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 × 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.
Keywords: Essential hypertension, arachidonic acid metabolism, cytochrome P450 CYP2J2, single nucleotide polymorphism, disease susceptibility, case-control studies
Journal: Disease Markers, vol. 24, no. 2, pp. 119-126, 2008
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