Interaction between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and environment with susceptibility to ischemic stroke in Chinese population

• Published in: Annals of the Indian Academy of Neurology 2020-07, Vol.23 (4), p.491-495
• Main Authors: Zheng, Xing-Zhen, Bian, Xiao-Lin, Sun, Zhe-Hong, Wang, Hai-Dong
• Format: Article
• Language: English
• Subjects: Alcohol; alcohol drinking; Alleles; Disease susceptibility; Drinking behavior; EDTA; Gene polymorphism; Genes; Genetic aspects; interaction; Ischemia; ischemic stroke; Methylenetetrahydrofolate reductase; Original; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Smoking; Statistical analysis; Stroke; Tobacco smoking
• ISSN: 0972-2327; 1998-3549
• DOI: 10.4103/aian.AIAN_192_19

Aims: To investigate the association of several single-nucleotide polymorphisms (SNPs) within methylenetetrahydrofolate reductase (MTHFR) gene, and additional gene-environment interaction with ischemic stroke (IS) risk. Methods: Testing for Hardy-Weinberg equilibrium in controls was conducted using SNPstats (online software: http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among four SNPs within MTHFR gene and smoking or alcohol drinking. Results: The frequency of the rs4846049-A allele was 28.6% in IS patients and 19.1% in normal controls, in addition, the frequency of the rs3737967-T allele was 27.9% in IS patients and 20.3% in normal controls, which was also indicating a statistically significant difference. The rs4846049-A and rs3737967-T were associated with an increased risk of IS risk; adjusted odds ratios (ORs) (95% confidence interval [CI]) were 1.76 (1.28-2.13) and 1.51 (1.13-1.97), respectively. GMDR model found significant gene-alcohol drinking interaction combination, but no significant gene-tobacco smoking interaction combinations. In order to obtain the odds ratios and 95% CI for the joint effects of gene-alcohol drinking on IS, we conducted stratified analysis for interaction effect using logistic regression. We found that alcohol drinkers with rs4846049-CA/AA genotype also have the highest IS risk, compared with never drinkers with rs4846049-CC genotype, OR (95% CI) = 3.12 (1.83-4.45), after adjustment for age, smoke, and smoking status. Conclusions: The rs4846049-A and rs3737967-T, gene-environment interaction between rs1764391 and rs918592, gene-environment interaction between rs4846049 and alcohol drinking were all associated with increased IS risk.