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The association between CYP1A1 genetic polymorphisms and coronary artery disease in the Uygur and Han of China.

ABSTRACT: The cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) gene is expressed in the vascular endothelium, which metabolizes arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs). 20-HETE mediates cardiovascular homeostasis and growth response in vascular smooth muscle cells (VSMCs) as well as the anti-platelet effect. EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. This study assessed the association between human CYP1A1 gene polymorphisms and coronary artery disease (CAD) in the Uygur and Han in China.Two independent case-control studies that recruited Han (389 patients with CAD and 411 controls) and Uygur participants (293 patients with CAD and 408 controls) analyzed the relationship between CYP1A1 single nucleotide polymorphisms (SNPs: rs4886605, rs12441817, rs4646422 and rs1048943) and CAD. All patients with CAD and controls were genotyped for the four SNPs of CYP1A1 using TaqMan SNP genotyping assays.In the Uygur group, the distribution of the dominant model(CC vs CT?+?TT) of rs4886605 for the total sample and the males was significantly different between CAD patients and control participants (P?=?0.001 and P?=?0.012, respectively), The difference remained significant after a multivariate adjustment (P?=?0.018, P?=?0.015, respectively). The rs12441817 was also associated with CAD in a dominant model for all participants (P?=?0.003) and men (P?=?0.012), and the difference remained significant after a multivariate adjustment (P?=?0.016, P?=?0.002, respectively). However, we did not observe differences in the Uygur females and Han group with regard to the allele frequency or genotypic distribution of rs4886605 and rs12441817 between patients with CAD and control participants. Patients with CAD did not significantly differ from the control participants with regard to the distributions of rs4646422 and rs1048943 genotypes, the dominant model, the recessive model, or allele frequency in the Han and Uygur groups.Both rs4886605 and rs12441817 SNPs of the CYP1A1 gene are associated with CAD in the Uygur population of China.

SUBMITTER: Zou JG

PROVIDER: S-EPMC4175619 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The association between CYP1A1 genetic polymorphisms and coronary artery disease in the Uygur and Han of China.

Zou Jin-Guo JG Ma Yi-Tong YT Xie Xiang X Yang Yi-Ning YN Pan Shuo S Adi Dilare D Liu Fen F Chen Bang-Dang BD

Lipids in health and disease 20140905

<h4>Background</h4>The cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) gene is expressed in the vascular endothelium, which metabolizes arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs). 20-HETE mediates cardiovascular homeostasis and growth response in vascular smooth muscle cells (VSMCs) as well as the anti-platelet effect. EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. This study assessed the a ...[more]

PMID: 25189712

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Project description:BACKGROUND: Endothelial cell activation and dysfunction are the foundation of atherosclerosis, including coronary artery disease (CAD). Endothelial cell activation is mediated by the level of gene transcription. Early growth response 3 (Egr3) is a critical determinant of vascular endothelial growth factor (VEGF) signalling in activated endothelial cells. If endothelial cells are excessively activated, it may lead to vasculopathic diseases, such as pathologic angiogenesis, inflammation, and atherosclerosis. The aim of the present study was to assess the association between the Egr3 gene polymorphisms and CAD. METHODS: Two independent case-control studies that involved the Han group (409 CAD patients and 351 control subjects) and the Uygur group (299 CAD patients and 303 control subjects) analysed the relationship between Egr3 SNPs (rs1996147 and rs1008949) and CAD. Genotyping was undertaken using the TaqMan SNP genotyping assay. RESULTS: The entire Uygur group and the males in the Uygur group showed a higher frequency of the A allele (rs1996147) in CAD patients than in the control subjects (P?=?0.003 and P?=?0.005, respectively). Additionally, the distribution of the recessive model of rs1996147 (AA vs GG?+?AG) for the total sample and the males was significantly different between CAD patients and control participants (P?=?0.002 and P?=?0.003, respectively), and the difference remained statistically significant following multivariate adjustment (Total: OR?=?1.705; 95% CI: 1.166-2.494, P?=?0.006; males: OR?=?1.908, 95% CI: 1.189-3.062, P?=?0.007). However, for Uygur females, we did not observe a difference in the allele frequency or genotypic distribution of rs1996147 between CAD patients and control participants. Similarly, the distribution of the rs1996147 allele frequency or genotypes showed no significant difference between patients with CAD and control participants in the Han group. The distribution of rs1008949 genotypes, dominant model, recessive model, and allele frequency did not show a significant difference between patients with CAD and the control subjects in the Han and Uygur groups. CONCLUSION: rs1996147 may be a novel polymorphism of the Egr3 gene associated with CAD in males of the Chinese Uygur population.

Project description:The morbidity of coronary artery disease (CAD) in the Uygur population of Xinjiang was much higher than the national average. Clopidogrel is the most commonly used medication worldwide in dual antiplatelet therapy for CAD, and the response of clopidogrel is affected by CYP2C19, PON1, and ABCB1 genetic polymorphisms. The distribution of CYP2C19*17, ABCB1, and PON1 genetic polymorphisms in Han and Uygur populations with CAD of Xinjiang has not been investigated.This study aimed to investigate the frequencies of CYP2C19, PON1, and ABCB1 genetic polymorphisms, and to identify the metabolizer phenotype of CYP2C19 in Han and Uygur populations with CAD in Northwestern Xinjiang, China. We identified 602 Han and 527 Uygur patients from 2014 through 2019 and studied genotypes for selected allele polymorphisms using sequencing by hybridization.There were significantly different allele frequencies and genotype frequencies between the 2 ethnic groups in terms of CYP2C19*2, *3, *17, ABCB1 and PON1, (P?<?.05). For CYP2C19*17, the frequency of TT genotype was 2.5% in Uygur patients, but it was undetectable in Han patients. In both the intermediate and poor metabolizer groups, the genotypes polymorphisms CYP2C19*2, *3, *17 were significantly less common in Uygur patients than in Han patients (P?<?.001). By contrast, the proportion of ultra-metabolizers as defined by CYP2C19*2, *3, *17 polymorphisms significantly higher in Uygur patients (18.6%) than in Han patients (1.7%, P?<?.001). The CYP2C19*2 frequency was significantly different between Han patients and Han healthy groups (P?<?.001), while the CYP2C19*3 frequency was significantly different between Uygur patients and Uygur healthy groups (P?<?.001).Our study supports the notion of interethnic differences in terms of CYP2C19, PON1, and ABCB1 polymorphisms and CYP2C19 genotype-defined clopidogrel metabolic groups. These finding could provide valuable data and insights into personalized CAD treatment for the Uygur and Han populations in Xinjiang.

Dataset Information

The association between CYP1A1 genetic polymorphisms and coronary artery disease in the Uygur and Han of China.

Publications

The association between CYP1A1 genetic polymorphisms and coronary artery disease in the Uygur and Han of China.

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