Association of Fetal MTHFR 677C > T Polymorphism with Non-Syndromic Cleft Lip with or without Palate Risk: A Systematic Review and Meta-Analysis

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.

Keywords:

• Cleft lip
• cleft palate
• MTHFR gene
• polymorphism
• meta-analysis

Acknowledgements

We are grateful to Professor Seyed Mehdi Kalantar and Professor Mohammad Hasan Sheikhha who kindly assisted the research.

Author contributions

All authors have directly participated in the planning or drafting of the manuscript and have read and approved the final version.

Conflict of interest

The authors declare no conflict of interest.