Maternal Betaine Homocysteine Methyltransferase Gene Polymorphism as a Risk Factor for Trisomy

Disorder in re-methylation process of homocysteine to methionine due to mutation in betaine homocysteine methyltransferase enzyme (BHMT) coding gene, leads to decrease in S-adenosyl methionine (SAM) synthesis which takes part in DNA methylation as a methyl donor. As a result, it can promote hypo-methylation of DNA, chromosome instability, and chromosome missegregation, which in turn is one of the main risk factors in trisomy 21 occurrence. The aim of this study was to investigate the distribution of BHMT polymorphism among mothers of Down syndrome and normal children. Genomic DNA extracted from blood samples of 45 mothers with at least one child presenting Down syndrome, as test group, and 30 mothers without affected children, as control group. G>A Single nucleotide polymorphism rs3733890 was investigated by PCR-RFLP method. The frequency of A allele was 37% in test group and 20% in control group. The frequency of G allele was 63% and 80% in test and control groups, respectively. The abundance of homozygous GG genotype was higher in control group (P= 0.03 ORGG = 1 and ORAA, AG = 1.4). Higher frequency of A allele in mothers with children affected with Down syndrome compared to control group, indicates that there might be an involvement of BHMT gene polymorphism in chromosomal nondisjunction leading to trisomy 21 children birth.