Methylenetetrahydrofolate Reductase C677T Polymorphism And The Risk Of Unexplained Recurrent Spontaneous Abortion:A Meta-analysis

Objective: To investigate the association between the methylenetetrahydrofolate reductase MTHFR(C677T)gene polymorphism and the risk of unexplained recurrent spontaneous abortion(URSA)by Meta analysis.Methods: We searched PubMed,EMbase,CNKI,VIP and WanFang Data from inception to August 2018 to collect case�control studies about the association between the MTHFR C677 T gene polymorphisms and the risk of URSA.The related literature was screened,the quality was evaluated and the basic data of the related case-control studies were extracted.Meta analysis was performed using Stata/SE 12.0.The correlation between the two was analyzed by testing the heterogeneity and calculating the combined ratio(Odds Ratio,OR)and 95% confidence interval(Confidence Interval,CI).Results: A total of 49 case-control studies involving 5774 URSA patients and 6338 controls were included.Total Meta analysis showed that MTHFR C677 T polymorphism was associated with the risk of URSA,and T allele carriers had 62% higher of developing URSA than C allele carriers,with ORvalue of 1.62 [95%CI(1.42,1.83)].MTHFR C677 T polymorphism was associated with the risk of URSA in Asian women.T allele carriers had 74%higher risk of developing URSA than C allele carriers,wtih OR value of 1.74[95%CI(1.52,1.98)].Women with TT genotype had 206% higher risk of developing URSA than those with CC genotype,and 125% higher risk of developing URSA than those with CT or CC genotype.In Non-Asian population,the results showed significant difference in gene model(TT vs CT +CC)(P = 0.03 <0.05),but not in the other gene models(TT vs CC,CT vs CC,TT + CT vs CC,T vs C)(P <0.05,0.155,0.645,0.594,respectively).In Chinese population,the results showed that there was a positive correlation between MTHFR C677 T gene polymorphism and risk of URSA.Women with TT and CT genotype had 215% and 63% higher risk of developing URSA than women with CC genotype,respectively,with OR value of 3.15 [95%CI(2.66,3.73)] and 1.63[95%CI(1.44,1.85)].Women with TT or CT genotype,respectively had 95%higher risk of developing URSA than women with CC genotype,with OR value of 1.95 [95%CI(1.74,2.19)].Women with TT genotype had 134% higher risk of developing URSA than women with CC or CT genotype,with OR value of 2.34[95%CI(2.03,2.69)].T allele carriers had 79% higher risk of developing URSA than C allele carriers,with OR value of 1.79 [95%CI(1.65,1.93)].Conclusion: The results showed significant association between the MTHFR C677 T polymorphism and the URSA in Asia population,but not in non-Asian population.And there is an association between the MTHFR C677 T polymorphism and the URSA in Chinese population,particularly TT and CT genotype is a high risk factor for URSA in Chinese women.