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Cleft lip/palate is one of the most common congenital defects and is supposed to have multifactorial etiology, including a complex interaction between genetics and environment. Reduced folate carrier 1 ( RFC1 ) gene takes part in folate transportation within the cells. In this study, the association of A80G polymorphism in the RFC1 gene with the non-syndromic cleft lip/palate (nsCL/P) was investigated in Iranian infants for the first time.  Methods:  In this case-control survey, 122 Iranian infants with nsCL/P and 164 healthy infants were investigated for RFC1 polymorphism by PCR and RFLP methods. The results were statistically compared with control group, odds ratios with 95% CI were estimated by univariate and multivariate logistic regression model and a P &lt;0.05 was considered statistically significant.  Results:  The RFC1 G allele was significantly higher ( P =0.001; OR=7, 95% CI: 4.7-10.2) in the cases (60.3%) compared with the controls (17.9%). Not only the RFC1 AG genotype was significantly higher ( P &lt;0.001; OR=44, 95% CI: 14.6-133) in cases (67.8%) than the controls (27.4%), but also GG genotype ( P &lt;0.001; OR=85, 95% CI: 20.5-352) was much higher in cases (26.4%) than the controls (4.3%).  Conclusion:  Our study indicated that the RFC1 (A80G) polymorphism was associated with the nsCL/P in Iranian population. Moreover, 80GG homozygosity was significant in the cases. The presence of G allele can be considered as a risk factor for the nsCL/P. Infants with the GG and AG genotypes were more prone to cleft lip/palate as compared to the AA ones. This finding emphasizes the role of RFC1 gene and the intracellular levels of folate.

The study of association between reduced folate carrier 1 (RFC1) polymorphism and non-syndromic cleft lip/palate in Iranian population