Maternal Gene Polymorphisms Involved in Folate Metabolism as Risk Factors for Down Syndrome Offspring in Southern Brazil

This study aimed to investigate the role of maternal polymorphisms, as well as their risk genotypes combinations ofMTRA2756G,MTRRA66G,CBS844ins68, andRFCA80G, involved in folate/homocysteine metabolism, as possible risk factors for Down syndrome (DS) in Southern Brazil. A case-control study was conducted with 239~mothers of DS children and 197 control mothers. The investigation of polymorphisms was performed by PCR and PCR-RFLP. The distribution of genotypic variants was similar in both groups when they were analyzed separately. An investigation of combined risk genotypes showed that the risk of having a DS child for one, two or three risk genotypes was 6.23, 6.96 and 5.84 (95%CI 1.48–26.26; 1.69–28.66; 1.37–24.86), respectively. The combinedMTRR66G andMTHFR677T alleles were significantly more common among mothers of children with DS than among control mothers (OR 1.55; IC 95% 1.03–2.35). The results show that individual polymorphisms studied in this work are not associated with DS; however, the effects of the combined risk genotypes amongMTR, MTRR, CBSandRFCgenes are considered maternal risk factors for DS offspring in our population.