DNA (cytosine-5)-methyltransferase 3B (DNMT 3B) polymorphism and risk of Down syndrome offspring.

ABSTRACT: Down syndrome (DS) is the most common form of human genetic mental retardation. Several polymorphisms in genes coding folic acid cycle enzymes have been associated to the risk of bearing a DS child; however, the results are controversial. S-adenosyl-l-methionine (SAM) is an important intermediate of folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5)-methyltransferase 3B (DNMT3B - EC 2.1.1.37) de novo methylation processes during embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B in maternal genotype may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 111 mothers of DS infants (MDS) and 212 control mothers (CM) through PCR-RFLP. The observed genotypic frequencies were CC = 0.22; CT = 0.49 and TT = 0.29 in CM, and CC = 0.30; CT = 0.52 and TT = 0.18 in MDS. Allelic frequencies were C = 0.47 and T = 0.53 in CM and C = 0.56 and T = 0.44 in MDS. No deviation of HWE was observed, and both DNMT 3B rs2424913 genotype (?2 = 4.53; DF = 1; P = 0.03) and allelic (?2 = 4.90; DF = 1; P = 0.03) frequencies show significant differences between MDS and CM. The presence of the mutant DNMT 3B T allele decreases 30% the risk of bearing a DS child (OR = 0.69; 95% CI: 0.50-0.96; P = 0.03), and the risk is diminished up to 45% in association with the homozygous genotype (OR = 0.54; 95% CI: 0.31-0.96; P = 0.04). Our results suggest that women harboring the single nucleotide polymorphism DNMT 3B rs2424913 have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

SUBMITTER: Moura CM 

PROVIDER: S-EPMC5775107 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature