Association of CYP2J2 gene polymorphisms with ischemic stroke and stroke subtypes in Chinese population

Abstract

Background and purpose:Ischemic stroke (IS) is the main cause of mortality and disability among the old people in China and is a multifactorial disease influenced by many factors including genetic factors like the allele for CYP 2J2. It has been demonstrated that CYP2J2 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2J2-50G/T polymorphism and IS have reported conflicting results. Thus, our study aimed to examine the association between 4 variants in the CYP2J2 gene and the risk of IS and its subtypes, in the Chinese population.Materials and Methods:In this study, genotyping was performed by using polymerase chain reaction (PCR) sequencing for 202 IS patients and 206 age- and sex-matched controls. Odds ratios (ORs) and confidence interval (CI) were estimated by multivariate logistic regression and PCR results were confirmed by DNA sequencing. A meta-analysis was conducted to evaluate the association of CYP2J2–50G>T polymorphism with the risk of IS in Chinese population by calculating pooled OR.Results:We found this polymorphism was significantly associated with IS (17.82% vs. 10.68%, P = 0.039). Multiple logistic regression analysis revealed that GT genotype was associated with a significantly high risk of IS (OR = 2.32, 95% CI: 1.21–4.45, P = 0. 011) after adjustment for other confounding factors such as hypertension, diabetes, heart disease, smoking habit, family history, triglyceride and low-density lipoprotein levels. We also found a significant association of GT genotype with small artery occlusion (SAA) (P < 0.05; OR = 2.22; 95% CI: 1.043–4.72). Meta-analysis results also showed that the GT genotype carriers had a negative effect on the risk of IS in Chinese population with overall OR of 1.40 (95% CI: 1.06–1.84).Conclusion:The findings of the present study suggested that polymorphism in −50G/T position of CYP2J2 gene might be a risk factor for IS in Chinese population. Further large prospective studies were required to confirm these findings.

Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes

“…The CYP2J2*7 allele has also been found to be associated with increased risk of MI in a South Indian population [ 17 ]. Two different studies in Chinese Han populations found an association between CYP2J2*7 with increased risk of ischemic stroke [ 18 , 19 ]. The odds ratios obtained in these association studies were adjusted for other cardiovascular risk factors, such as age, gender, blood pressure, blood lipid levels, and body mass index.…”

Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review

“…Furthermore, some studies suggest that CYP variants mediating weaker AA metabolism can contribute to kidney damage ( 59 ) and that carriers of loss-of-function alleles CYP2C9 *2 and CYP2C9 *3 have reduced EET production ( 60 ). Furthermore, loss-of-function CYP2C8 *3, CYP2C9 *2, CYP2C9 *3, and CYP2J2 *7 variants have been associated with endothelial dysfunction, myocardial infarction, and stroke ( 61 , 62 , 63 , 64 ).…”

Present Status and Future Challenges of New Therapeutic Targets in Preclinical Models of Stroke in Aged Animals with/without Comorbidities

“…Genetic factors play an important role in the pathogenesis of cerebral ischemia. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms which have been associated with an increased risk of cerebral ischemia [ 56 , 57 , 58 , 59 , 60 , 61 ]. Previous studies also suggested that increased DNA damage occurs after cerebral ischemia [ 62 ].…”