MTHFR C677T and A1298C polymorphisms are not related to ventricular or atrial septal defect: a meta-analysis of 1272 cases and 1386 controls

作者：Zhang, Tiejuan^*; Wu, Qingqing

来源：International Journal of Clinical and Experimental Medicine, 2016, 9(6): 10673-10683.

• Methylenetetrahydrofolate reductase
• MTHFR
• C677T
• A1298C
• polymorphism
• ventricular septal defect
• atrial septal defect

Objective: Congenital heart defect (CHD), especially ventricular and atrial septal defects (VSD/ASD), is a severe neonatal disease affecting infants in both developing and developed countries. Ultrasonic exam is the best way to detect this disease. The study between related SNP (Single Nucleotide Polymorphism) has distinctly auxiliary value in CHD screening and diagnosis. Although many studies reported the association between MTHFR (methylenetetrahydrofolate reductase) polymorphisms and VSD/ASD risk, the results are controversial. Therefore, we conducted a meta-analysis of the published literature to identify the association between MTHFR Gene Polymorphism and Risk of VSD/ASD. Design: EMBASE, Web of science, PubMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched for articles that reported the association between MTHFR polymorphisms and VSD/ASD risk. Setting: The studies that focused on the relationship between C677T and C1298C polymorphisms and VSD/ASD risk were extracted for analysis. Patients: 1272 cases and 1386 controlsfrom 9 studies were included in our study. Interventions: Fixed-effect model or random-effect model was used to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI). The Begg's and Egger's test were used to assess publication bias. The forest plot was drawn by ethnicity. Sensitivity analyses were also performed to evaluate the robustness of the findings. Outcome Measures: The odd ratio of the association between MTHFR C677T and A1298C polymorphism and VSD/ASD risk was calculated in five genetic models. Results: The results of allele model (C vs. T) showed no significant association between MTHFR C677T and A1298C polymorphism and VSD/ASD risk (C677T Odd Ratio=0.96, 95% CI 0.74, 1.24, A1298C Odd Ratio=1.10, 95% CI 0.80, 1.51) in total population. Subgroup analysis by ethnicity and other four genetic models also did not show significant association. The limitation of the analysis was Hardy-Weinberg equilibrium in some studies demonstrated statistical significance, and Begg's funnel plot showed potential publication bias (P<0.01). Linkage disequilibrium analysis did not identify any polymorphism linkage with MTHFR C677T or A1298C. Conclusion: The meta-analysis suggested that MTHFR C677T and A1298C polymorphisms are not associated with the risk of ventricular or atrial septal defect.

• 出版日期2016
• 单位首都医科大学