Abstract

Background: The S-adenosyl-methionine (SAM) availability is crucial for DNA methylation, an epigenetic mechanism involved in nonsyndromic cleft lip with or without cleft palate (NSCL/P) expression. The aim of this study was to assess the association between single nucleotide polymorphisms (SNPs) of genes involved in SAM synthesis and NSCL/P in a Chilean population. Methods: In 234 cases and 309 controls, 18 SNPs in AHCY, MTR, MTRR and MAT2A were genotype and the association between them and the phenotype was evaluated based on additive (allele), dominant, recessive and haplotype models, by odds ratio (OR) computing. Results: three deep intronic SNPs of MTR showed a protective effect on NSCL/P expression: rs10925239 (OR 0.68; p=0.0032; q=0.0192), rs10925254 (OR 0.66; p=0.0018; q=0.0162) and rs3768142 (OR 0.66; p=0.0015; q=0.0162). Annotations in expression database demonstrate that the protective allele of the three SNPs are associated with a reduction of MTR expression summed to the prediction by bioinformatic tools of its potentiality to modify splicing sites. Conclusion: the protective effect against NSCL/P of these intronic MTR SNPs seems to be related to a decrease in MTR enzyme expression, modulating the SAM availability for proper substrate methylation. However, functional analyses are necessary to confirm our findings.