Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methylation in neuroprogenitors, which then persists in the fetal DS brain where DNMT3A and DNMT3B become downregulated.
The DNMT3B -579T allele [odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.48-0.94, P = 0.02], the DNMT3B -579 GT genotype (OR = 0.55; 95% CI = 0.35-0.87 , P = 0.01) and the combined DNMT3B -579 GT + TT genotype (OR = 0.55; 95% CI = 0.36-0.86 , P = 0.008) were associated with reduced risk of birth of a child with DS.
Considering 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.