A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease

A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease

Enzymes CYP4A11 and CYP4F2 are involved in biosynthesis of vasoactive 20-hydroxyeicosatetraenoic acid and may contribute to pathogenesis of coronary artery disease (CAD). We investigated whether polymorphisms of the CYP4A11 and CYP4F2 genes are associated with the risk of CAD in Russian population....

Full description

Bibliographic Details
Main Authors: Svetlana Sirotina, Irina Ponomarenko, Alexander Kharchenko, Marina Bykanova, Anna Bocharova, Kseniya Vagaytseva, Vadim Stepanov, Mikhail Churnosov, Maria Solodilova, Alexey Polonikov
Format: Article
Language:English
Published: Hindawi Limited 2018-01-01
Series:Disease Markers
Online Access:http://dx.doi.org/10.1155/2018/5812802
id doaj-ee571c21fb2348789d0d94059b38052d
record_format Article
spelling doaj-ee571c21fb2348789d0d94059b38052d2020-11-24T22:12:46ZengHindawi LimitedDisease Markers0278-02401875-86302018-01-01201810.1155/2018/58128025812802A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery DiseaseSvetlana Sirotina0Irina Ponomarenko1Alexander Kharchenko2Marina Bykanova3Anna Bocharova4Kseniya Vagaytseva5Vadim Stepanov6Mikhail Churnosov7Maria Solodilova8Alexey Polonikov9Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Karl Marx Street 3, Kursk 305041, RussiaDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University, Karl Marx Street 3, Kursk 305041, RussiaDepartment of Internal Medicine, Kursk State Medical University, 14 Pirogova St., Kursk 305035, RussiaLaboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Yamskaya Street 18, Kursk 305041, RussiaEvolutionary Genetics Laboratory, Research Institute of Medical Genetics, Tomsk National Research Medical Center, 10 Nabereznaya Ushaiki, Tomsk 634050, RussiaEvolutionary Genetics Laboratory, Research Institute of Medical Genetics, Tomsk National Research Medical Center, 10 Nabereznaya Ushaiki, Tomsk 634050, RussiaEvolutionary Genetics Laboratory, Research Institute of Medical Genetics, Tomsk National Research Medical Center, 10 Nabereznaya Ushaiki, Tomsk 634050, RussiaDepartment of Medical Biological Disciplines, Belgorod State University, 85 Pobeda St., Belgorod 308015, RussiaDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University, Karl Marx Street 3, Kursk 305041, RussiaDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University, Karl Marx Street 3, Kursk 305041, RussiaEnzymes CYP4A11 and CYP4F2 are involved in biosynthesis of vasoactive 20-hydroxyeicosatetraenoic acid and may contribute to pathogenesis of coronary artery disease (CAD). We investigated whether polymorphisms of the CYP4A11 and CYP4F2 genes are associated with the risk of CAD in Russian population. DNA samples from 1323 unrelated subjects (637 angiographically confirmed CAD patients and 686 age- and sex-matched healthy individuals) were genotyped for polymorphisms rs3890011, rs9332978, and rs9333029 of CYP4A11 and rs3093098 and rs1558139 of CYP4F2 by using the Mass-ARRAY 4 system. SNPs rs3890011 and rs9332978 of CYP4A11 were associated with increased risk of CAD in women: OR = 1.26, 95% CI: 1.02–1.57, P=0.004, and Q=0.01 and OR = 1.45, 95% CI: 1.13–1.87, P=0.004, and Q=0.01, respectively. Haplotype G-C-A of CYP4A11 was associated with increased risk of CAD (adjusted OR = 1.41, 95% CI: 1.12–1.78, and P=0.0036). Epistatic interactions were found between rs9332978 of CYP4A11 and rs1558139 of CYP4F2 (Pinteraction=0.025). In silico analysis allowed identifying that SNP rs9332978 is located at a binding site for multiple transcription factors; many of them are known to regulate the pathways involved in the pathogenesis of CAD. This is the first study in Europeans that reported association between polymorphism rs9332978 of CYP4A11 and susceptibility to coronary artery disease.http://dx.doi.org/10.1155/2018/5812802
collection DOAJ
language English
format Article
sources DOAJ
author Svetlana Sirotina
Irina Ponomarenko
Alexander Kharchenko
Marina Bykanova
Anna Bocharova
Kseniya Vagaytseva
Vadim Stepanov
Mikhail Churnosov
Maria Solodilova
Alexey Polonikov
spellingShingle Svetlana Sirotina
Irina Ponomarenko
Alexander Kharchenko
Marina Bykanova
Anna Bocharova
Kseniya Vagaytseva
Vadim Stepanov
Mikhail Churnosov
Maria Solodilova
Alexey Polonikov
A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease
Disease Markers
author_facet Svetlana Sirotina
Irina Ponomarenko
Alexander Kharchenko
Marina Bykanova
Anna Bocharova
Kseniya Vagaytseva
Vadim Stepanov
Mikhail Churnosov
Maria Solodilova
Alexey Polonikov
author_sort Svetlana Sirotina
title A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease
title_short A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease
title_full A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease
title_fullStr A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease
title_full_unstemmed A Novel Polymorphism in the Promoter of the CYP4A11 Gene Is Associated with Susceptibility to Coronary Artery Disease
title_sort novel polymorphism in the promoter of the cyp4a11 gene is associated with susceptibility to coronary artery disease
publisher Hindawi Limited
series Disease Markers
issn 0278-0240
1875-8630
publishDate 2018-01-01
description Enzymes CYP4A11 and CYP4F2 are involved in biosynthesis of vasoactive 20-hydroxyeicosatetraenoic acid and may contribute to pathogenesis of coronary artery disease (CAD). We investigated whether polymorphisms of the CYP4A11 and CYP4F2 genes are associated with the risk of CAD in Russian population. DNA samples from 1323 unrelated subjects (637 angiographically confirmed CAD patients and 686 age- and sex-matched healthy individuals) were genotyped for polymorphisms rs3890011, rs9332978, and rs9333029 of CYP4A11 and rs3093098 and rs1558139 of CYP4F2 by using the Mass-ARRAY 4 system. SNPs rs3890011 and rs9332978 of CYP4A11 were associated with increased risk of CAD in women: OR = 1.26, 95% CI: 1.02–1.57, P=0.004, and Q=0.01 and OR = 1.45, 95% CI: 1.13–1.87, P=0.004, and Q=0.01, respectively. Haplotype G-C-A of CYP4A11 was associated with increased risk of CAD (adjusted OR = 1.41, 95% CI: 1.12–1.78, and P=0.0036). Epistatic interactions were found between rs9332978 of CYP4A11 and rs1558139 of CYP4F2 (Pinteraction=0.025). In silico analysis allowed identifying that SNP rs9332978 is located at a binding site for multiple transcription factors; many of them are known to regulate the pathways involved in the pathogenesis of CAD. This is the first study in Europeans that reported association between polymorphism rs9332978 of CYP4A11 and susceptibility to coronary artery disease.
url http://dx.doi.org/10.1155/2018/5812802
work_keys_str_mv AT svetlanasirotina anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT irinaponomarenko anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT alexanderkharchenko anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT marinabykanova anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT annabocharova anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT kseniyavagaytseva anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT vadimstepanov anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT mikhailchurnosov anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT mariasolodilova anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT alexeypolonikov anovelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT svetlanasirotina novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT irinaponomarenko novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT alexanderkharchenko novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT marinabykanova novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT annabocharova novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT kseniyavagaytseva novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT vadimstepanov novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT mikhailchurnosov novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT mariasolodilova novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
AT alexeypolonikov novelpolymorphisminthepromoterofthecyp4a11geneisassociatedwithsusceptibilitytocoronaryarterydisease
_version_ 1725802467218685952

Similar Items