Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese PopulationReport as inadecuate




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Ischemic stroke IS is a multifactorial disorder caused by both genetic and environmental factors. The combined effects of multiple susceptibility genes might result in a higher risk for IS than a single gene. Therefore, we investigated whether interactions among multiple susceptibility genes were associated with an increased risk of IS by evaluating gene polymorphisms identified in previous meta-analyses, including methylenetetrahydrofolate reductase MTHFR C677T, beta fibrinogen FGB, β-FG A455G and T148C, apolipoprotein E APOE ε2–4, angiotensin-converting enzyme ACE insertion-deletion I-D, and endothelial nitric oxide synthase eNOS G894T. In order to examine these interactions, 712 patients with IS and 774 controls in a Chinese Han population were genotyped using the SNaPshot method, and multifactor dimensionality reduction analysis was used to detect potential interactions among the candidate genes. The results of this study found that ACE I-D and β-FG T148C were significant synergistic contributors to IS. In particular, the ACE DD + β-FG 148CC, ACE DD + β-FG 148CT, and ACE ID + β-FG 148CC genotype combinations resulted in higher risk of IS. After adjusting for potential confounding IS risk factors age, gender, family history of IS, hypertension history and history of diabetes mellitus using a logistic analysis, a significant correlation between the genotype combinations and IS patients persisted overall stroke: adjusted odds ratio OR = 1.57, 95% confidence interval CI: 1.22–2.02, P < 0.001, large artery atherosclerosis subtype: adjusted OR = 1.50, 95% CI: 1.08–2.07, P = 0.016, small-artery occlusion subtype: adjusted OR = 2.04, 95% CI: 1.43–2.91, P < 0.001. The results of this study indicate that the ACE I-D and β-FG T148C combination may result in significantly higher risk of IS in this Chinese population.



Author: Man Luo , Jiaoxing Li , Xunsha Sun , Rong Lai, Yufang Wang, Xiaowei Xu , Wenli Sheng

Source: http://plos.srce.hr/



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