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

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Listed:
  • Man Luo
  • Jiaoxing Li
  • Xunsha Sun
  • Rong Lai
  • Yufang Wang
  • Xiaowei Xu
  • Wenli Sheng

Abstract

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

Suggested Citation

  • Man Luo & Jiaoxing Li & Xunsha Sun & Rong Lai & Yufang Wang & Xiaowei Xu & Wenli Sheng, 2015. "Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese Population," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-10, December.
    • Handle: RePEc:plo:pone00:0145399
    DOI: 10.1371/journal.pone.0145399
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    References listed on IDEAS

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    1. Meiyun Wang & Xiubo Jiang & Wenlong Wu & Dongfeng Zhang, 2013. "Endothelial NO Synthase Gene Polymorphisms and Risk of Ischemic Stroke in Asian Population: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-9, March.
    2. Landin Boring & Jennifa Gosling & Michael Cleary & Israel F. Charo, 1998. "Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis," Nature, Nature, vol. 394(6696), pages 894-897, August.
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