Genetic polymorphism of MTHFR C677T and premature coronary artery disease susceptibility: A meta-analysis

• It's the first meta-analysis to evaluate association between MTHFR C677T and PCAD.
• PCAD may cause heavier burden on the health system than conventional CAD.
• Co-dominant, dominant, recessive models and allele analysis were all performed.
• Subgroup analyses were conducted by Hcy level, continent and source of controls.

The association between 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and premature coronary artery disease (PCAD) is controversial. To explore a more precise estimation of the association, a meta-analysis was conducted in the present study. The relevant studies were identified by searching PubMed, EMBASE, the Web of Science, Cochrane Collaboration Database, Chinese National Knowledge Infrastructure, Wanfang Database and China Biological Medicine up to November, 2014. The meta-analysis was performed by STATA 11. 21 studies with a total of 6912 subjects, including 2972 PCAD patients and 3940 controls. The pooled analysis showed that MTHFR C677T gene polymorphism was probably associated with PCAD (CT vs. CC: OR = 1.13, 95% CI = 1.01–1.27; dominant model: OR = 1.16, 95% CI = 1.04–1.29; recessive model: OR = 1.19, 95% CI = 1.00–1.40; allele analysis: OR = 1.17, 95% CI = 1.01–1.34). Subgroup analysis by plasma homocysteine concentration showed a significant association in the homocysteine > 15 μmol/L subgroup (CT vs. CC: OR = 1.44, 95% CI = 1.10–1.88; TT vs. CC: OR = 2.51, 95% CI = 1.12–5.63; dominant model: OR = 1.51, 95% CI = 1.16–1.96; recessive model: OR = 2.33, 95% CI = 1.05–5.20; allele analysis: OR = 1.48, 95% CI = 1.18–1.87). Subgroup analysis by continent displayed a significant association among the Asian population (CT vs. CC: OR = 1.51, 95% CI = 1.23–1.86; TT vs. CC: OR = 2.81, 95% CI = 1.87–4.23; dominant model: OR = 1.65, 95% CI = 1.35–2.01; recessive model: OR = 2.22, 95% CI = 1.53–3.21; allele analysis: OR = 1.61, 95% CI = 1.37–1.89). The statistical stability and reliability was demonstrated by sensitivity analysis and publication bias outcomes. In conclusion, the meta-analysis suggests that MTHFR C677T gene polymorphism may be associated with PCAD.