Association of RFC1 A80G Gene Polymorphism with Nonsyndromic Cleft Lip and Palate in Hispanics from Venezuela and Guatemala

Objective: Investigate association of single nucleotide polymorphism rs1051266 on 80th nucleotide of reduced folate carrier 1 (RFC1) gene with non-syndromic cleft lip with or without cleft palate (nsCL±P). Materials and Methods: A case-control study design was used for this study. Samples of cases (188 individuals with nsCL±P) and controls (157 individuals) were Hispanics from Venezuela and Guatemala. Genomic DNA was extracted from blood spots on filter paper. RFC1-A80G genotypes were established using polymerase chain reaction and polyacrylamide gel electrophoresis. Results: Statistically significant higher proportion of mutated homozygotes GG and the lower homozygotes AA were found in cases compared to controls (p=.0234). Also, A and G allele frequencies were significantly different (p=.0088). When each location was evaluated separately the highly significant differences were observed only in Guatemalan but not in Venezuelan subsample. Conclusions: Our study showed that RFC1-A80G variant may contribute to the etiology of nsCL±P. It revealed differences in RFC1-A80G polymorphism frequencies in populations from different locations. A strong association of RFC1-A80G polymorphism with nsCL±P was observed in the population from Guatemala City, Guatemala only. We have shown that lumping together samples from different populations could hide differences in genotype and allele frequencies in individual populations.