BackgroundEpigenetic changes leading to improper methylation of the pericentromeric region of chromosome 21 may contribute to the nondisjunction of this chromosome. Polymorphisms in the DNA Methyltransferase 3B (DNMT3B) gene, one of the crucial gene of the folate metabolism, affects the activity of the enzyme and increases the susceptibility of nondisjunction in mothers of Down syndrome children (MDS).MethodsConsidering this hypothesis we investigated the association of single nucleotide polymorphisms in the promoter region of the DNMT3B gene (rs1569686 ‐579G>T; rs2424913 ‐149C>T) with a predisposition of mothers to deliver a Down syndrome (DS) child. The study was performed on DNA samples from 150 MDS and 172 control mothers. Transmission disequilibrium tests were performed on 103 DS trio families. Genotyping was done using a polymerase chain reaction‐restriction fragment length polymorphism method.ResultsWith respect to the single nucleotide polymorphisms studied, no significant difference was observed in the genotypes and alleles frequency distributions between MDS and control mothers. The frequency of the DNMT3B‐579G allele was, respectively, 0.34 in MDS and 0.33 in control mothers whereas the frequency of the DNMT3B‐149C allele was respectively 0.31 in MDS and 0.26 in control mothers. No significant deviation in genotypic combinations as well as in transmission disequilibrium tests analysis was observed. However, a strong linkage disequilibrium was observed with significant differences in the distribution of G‐T and G‐C haplotypes among case and control mothers.ConclusionAlthough the above studied polymorphisms of DNMT3B may not be an independent risk factor it might be possible that certain allelic combinations (G‐T) are. This finding suggests that DNMT3B might be a maternal risk factor for DS in our Indian cohort. Replication studies are required to confirm these findings. Birth Defects Research (Part A) 103:299–305, 2015. © 2015 Wiley Periodicals, Inc.