Reduced Folate Carrier Gene Polymorphism in Six Orofacial Cleft Samples

INTRODUCTION: RFC1 (reduced folate carrier 1) gene encodes a cell membrane protein essential for internalizing folate bound to a folate-binding protein from circulating blood into cells. The active form of folate is essential for multiplication, differentiation and maintenance of cells. Thus, when there is a defect in the metabolism of such a vital vitamin, or when the mother is not ingesting enough of this vitamin, congenital anomalies in the fetus may occur.

OBJECTIVES: To compare frequencies of A80G variants of RFC1 gene in orofacial cleft samples from different locations.

MATERIAL AND METHODS: Blood specimens were collected during Rotaplast medical missions from 564 individuals affected with nonsyndromic cleft lip and palate (NCLP) and from 484 controls in 6 locations: Santiago del Estero, Argentina; Valdivia and Antofagasta, Chile; Guatemala City, Guatemala; Barquisimeto and Cumana, Venezuela, over the past 7 years. PCR followed by PAGE were used for genotyping of the RFC1 A80G polymorphism.

RESULTS: Distributions of RFC1 A80G genotypes and frequencies of A and G alleles were calculated. The highest G (mutated) allele frequency was found among cases in Guatemala City (p=0.016 for GG genotypes and p=0.010 for G allele, when compared to controls) followed by Santiago del Estero (p=0.030 for GG genotypes and p=0.037 for G allele). In Valdivia, only the difference in G allele frequency was significant (p=0.026). The differences between cases and controls were not statistically significant in the remaining locations, although the G allele frequencies among cases were higher than controls in all locations.

CONCLUSIONS: The G allele in nucleotide 80 of the RFC1 gene was more common in individuals with NCLP than in controls from the same locations. The difference between cases and controls was statistically significant in 3 out of 6 studied samples.

ACKNOWLEDGEMENT: Rotaplast International, Inc., supported the fieldwork for this study.