Association Between MTHFR C677T Polymorphism and Congenital Heart Disease
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Published on: May 5, 2018
Peng-Fei Liu1, Bing Ding1, Jun-Yi Zhang1
1Department of Cardiology, The First Affiliated Hospital of Soochow University.
Insights
The 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene variant increases congenital heart disease (CHD) risk, particularly in Asian populations. This meta-analysis confirms MTHFR C677T as a risk factor for CHD development.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Research
- Public Health and Epidemiology
Background:
- The association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and congenital heart disease (CHD) risk remains controversial.
- Previous studies have yielded conflicting results, necessitating a comprehensive re-evaluation.
- Understanding genetic predispositions like MTHFR C677T is crucial for CHD etiology research.
Purpose of the Study:
- To conduct a meta-analysis to definitively evaluate the association between the MTHFR C677T polymorphism and the risk of congenital heart disease (CHD).
- To clarify the controversial findings from individual studies.
- To explore potential subgroup differences based on ethnicity and control sources.
Main Methods:
- A systematic literature search was performed across major databases (PubMed, Embase, Web of Science, etc.).
- Fifteen eligible studies were included, with quality assessed using the Newcastle-Ottawa Scale (NOS).
- Meta-analysis, heterogeneity testing, subgroup analyses (ethnicity, control source, etc.), sensitivity analysis, and publication bias assessment (Egger's test, Begg's funnel plot) were employed.
Main Results:
- A significant correlation was observed between the MTHFR C677T polymorphism and CHD risk in the recessive model for the overall population (OR: 1.35, 95% CI: 1.06-1.71, P = 0.006).
- Subgroup analyses revealed significant associations in Asians and hospital-based control groups, but not in Caucasians or population-based control groups.
- No significant publication bias was detected.
Conclusions:
- The MTHFR C677T polymorphism is identified as a risk factor for the development of congenital heart disease (CHD).
- The risk associated with the MTHFR C677T allele is particularly pronounced in Asian populations compared to Caucasians.
- These findings contribute to a better understanding of the genetic underpinnings of CHD.
Abstract:
Many published studies have evaluated the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) polymorphism and the risk of congenital heart disease (CHD); however, the specific conclusion is still controversial.To get a more accurate conclusion, we used a meta-analysis to evaluate the association between the MTHFR gene C677T polymorphism and the risk of CHD.Based on the design-based search strategy, a comprehensive literature search was conducted on PubMed, OVID, Cochrane Library, Embase, Wanfang, CNKI, and Web of Science. We selected the Newcastle-Ottawa Scale (NOS) to assess the quality of the included studies. We performed a heterogeneity test on the results of the study and calculated the combined odds ratios (ORs) and its corresponding 95% confidence intervals (95% CIs) under a random- or fixed-effect model. Subgroup analyses were conducted by ethnicity, source of controls, sample size, and genotyping method. Sensitivity analysis was used to insure authenticity of this meta-analysis result. Egger's test and Begg's funnel plot were performed to detect publication bias.Eventually, our meta-analysis included 15 eligible studies. We observed a significant correlation between the MTHFR C677T polymorphism and the development of CHD in the recessive model (OR: 1.35, 95% CI: 1.06-1.71, P = 0.006) for the overall population. In subgroups stratified by ethnicity and source of controls, subgroup analyses indicated similar associations in Asians and hospital-based groups, but not for Caucasians and population-based groups. Egger's test and Begg's funnel plot demonstrated no significant publication bias in our study.Our analysis identified that MTHFR C677T allele is a risk genetic for CHD development, especially in Asians compared with Caucasians.
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