Abstract

Background: This study was conducted to estimate the precise association of fetal MTHFR 677 C > T polymorphism with risk of nonsyndromic cleft lip with or without cleft palate (NSCL +/- P) using a large-scale meta-analysis. Methods: A comprehensive literature search was performed using studies published on PubMed, Science Direct, Scopus and CNKI databases up to November 1, 2019. Results: A total of 38 studies with 6,525 children with NSCL +/- P and 8,606 controls were selected. Overall, there was a significant association between MTHFR 677 C > T polymorphism and NSCL +/- P risk. Subgroup analysis by ethnicity revealed that MTHFR 677 C > T polymorphism contributed to development of NSCL +/- P in Caucasian and Mixed populations, but not in Asians. When stratified by country of origin, we found a significant association in Brazilian, Turkish and Indian populations, but not in Chinese and US-American. Conclusions: This meta-analysis provides strong evidence that fetal MTHFR 677 C > T polymorphism is significantly associated with NSCL +/- P risk.