MTHFR c.677C>T is a risk factor for non‐syndromic cleft lip with or without cleft palate in Chile

Objective The functional variant within the 5,10‐methylenetetrahydrofolate reductase ( MTHFR ) gene c.677C>T, producing alterations in folate metabolism, has been associated with the risk of non‐syndromic cleft lip with or without cleft palate ( NSCL /P). We assessed this association in a Chilean population using a combined analysis of case–control and case–parent trio samples. Subjects and methods Samples of 165 cases and 291 controls and 121 case–parent trios (sharing the cases) were genotyped. Odds ratio ( OR ) was estimated for case–control (allele and genotype frequency differences), and this result was confirmed by allele transmission distortion in trios. Due to that these samples are not independent, a combined OR was also computed. Maternal genotype effect was additionally evaluated based on a log‐linear method. Results Borderline but not significant OR (1.28; CI 0.97–1.69) was observed for risk allele (T) in the case–control sample. However, triad sample showed a significant association ( OR 1.56: CI 1.09–2.25) which was confirmed by the combined OR (1.37; CI 1.11–1.71). Maternal genotype has been also associated with the phenotype ( P  = 0.002). Conclusions In contrast to previous reports considering Chilean subjects, our results demonstrated that the offspring and maternal genotypes for MTHFR c.677C>T variant are strongly associated with NSCL /P in this Chilean population.