Association of RFC1 A80G gene polymorphism with advanced maternal age in risk of Down Syndrome

Background: Down Syndrome (DS) is a serious intellectually disabled condition and a major public health concern. Advanced maternal age and altered recombination are the well established factors for its cause. Epidemiological studies have reported conflicting results regarding the association between maternal folate gene polymorphism, folic acid supplementation and the risk of DS. Aim of the Study: The investigation present a case–control study of polymorphisms in four genes (MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G and RFC1 A80G) involved in folate pathway and assessment of folate supplementation and association of age during conception. Materials and Methods: We investigated 148 DS mothers and 130 control mothers from India. Allele specific primers were used for the analysis of gene polymorphisms, and folic acid supplementation profile was also recorded. Results: Association of RFC1 80GG genotype (3.2579, 95% CI: 1.5363–6.9086, p = 0.0021) with DS indicating increased risk in developing DS. A significant association was also found between maternal age of ≥34 years and RFC1 80G alleles in developing DS. Folic acid supplementation profile indicated non-supplementation of folic acid preconception leads to an increase (1.6904, 95% CI: 1.0730–2.6631, p = 0.0236) in risk of DS. Conclusion: The present investigation suggests the potential role of RFC1gene polymorphism in folate metabolism in association with maternal age and dietary folate deficiency preconception increases the risk of DS