Polymorphism of reduced folate carrier 1 (A80G) and non-syndromic cleft lip/palate: A systematic review and meta-analysis

Objective: To evaluate the association between polymorphism of reduced folate carrier 1 (RFC1) A80 G in infants and the risk of non-syndromic cleft lip/palate (NSCL/P), in a meta-analysis of case-control studies. Design: We searched databases of PubMed, Scopus, Web of Science, and Cochrane Library for studies on the association of mentioned polymorphism and NSCL/P risk published until August 2018. Results: Seven articles were selected based on the criteria and were analyzed in this meta-analysis (1486 NSCL/P patients and 1596 controls). Overall, it was not obtained a significant association between the polymorphism and NSCL/P risk, with the exception of the recessive model (odds ratio = 1.45; 95% confidence interval = 1.03, 2.05; P = 0.03). A subgroup analysis showed that the frequency of GG genotype in the homozygote and recessive models in the Caucasian ethnicity was significantly higher in NSCL/P patients than in controls. Sensitivity analysis showed that the frequency of G allele and GG genotype in NSCL/P cases was significantly higher than that in controls. Conclusions: The results identified an association between the GG genotype and NSCL/P risk and just confirmed this association in the Caucasian ethnicity. Therefore, the GG genotype of RFC1 (A80 G) polymorphism can be related to NSCL/P risk in some ethnicities more than others.