Polymorphisms of CYP2C8, CYP2C9 and CYP2C19 and risk of coronary heart disease in Russian population

Autor: A. V. Bocharova, Mikhail Churnosov, Alexander Kharchenko, Alexey Polonikov, Maria Solodilova, Vadim Stepanov, Svetlana Sirotina, Olga Bushueva, Kseniya Vagaytseva, Irina Ponomarenko, Marina Bykanova
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Россия
полиморфизм единичного нуклеотида
эпоксиэйкозатриеновые кислоты
Single-nucleotide polymorphism
Coronary Disease
CYP2C19
030204 cardiovascular system & hematology
Biology
Bioinformatics
Polymorphism
Single Nucleotide
Russia
Cytochrome P-450 CYP2C8
03 medical and health sciences
0302 clinical medicine
Genetics
Genetic predisposition
SNP
Humans
CYP2C8
CYP2C9
генетическая восприимчивость
Aged
Cytochrome P-450 CYP2C9
ишемическая болезнь сердца
General Medicine
Odds ratio
Middle Aged
Cytochrome P-450 CYP2C19
030104 developmental biology
Genetic marker
Case-Control Studies
метаболизм арахидоновой кислоты
цитохром P450
Female
Zdroj: Gene. 2017. Vol. 627. P. 451-459
ISSN: 1879-0038
6188-6769
Popis: Epoxyeicosatrienoic acids (EETs) are important vasoactive products of arachidonic acid metabolism with a wide range of biological actions in the cardiovascular system. The present study investigated whether single nucleotide polymorphisms (SNP) of genes coding cytochrome P450 2C subfamily, enzymes involved in biosynthesis of EETs, are associated with the risk of coronary heart disease (CHD). A total of 1255 unrelated Russian subjects comprising 561 patients with angiographically diagnosed CHD and 694 age- and sex-matched healthy subjects were included in the study. DNA samples from all study participants were genotyped for six common SNPs rs7909236, rs1934953 of CYP2C8, rs9332242, rs4918758 and rs61886769 of CYP2C9 and rs4244285 of CYP2C19 using by the Mass-ARRAY 4 system. SNP rs4918758 of CYP2C9 was associated with decreased risk of CHD (codominant model) at a borderline significance with odds ratio adjusted for sex and age 0.61 (95% CI: 0.41–0.92, P = 0.038, Q = 0.20). SNP rs9332242 of CYP2C9 showed a trend towards association with increased CHD risk in cigarette smokers (P = 0.049, Q = 0.29). Log-likelihood ratio test (LRT) pointed out epistatic interactions between rs9332242 and rs61886769 of CYP2C9 (codominant model, Pinteraction = 0.02), however, this P-value did not survive after correction for multiple tests. Bioinformatic analysis revealed a regulatory potential for a majority of the investigated SNPs. Our preliminary results demonstrate that polymorphisms of genes encoding CYP2C subfamily represent potential genetic markers of CHD susceptibility. Further studies are required to substantiate the contribution of these genes to the disease risk.
Databáze: OpenAIRE
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