Meta-analyses of published data have already been performed to overcome the limits of tiny case-control cohorts, revealing that each the methylenetetrahydrofolate reductase (MTHFR c.677C>T) as well as the Title Loaded From File methionine Title Loaded From File synthase reductase (MTRRNutrients 2013,c.66A>G) polymorphisms (both genes are involved in folate metabolism) could possibly represent independent maternal threat elements for the birth of a youngster with DS [15?7]. These papers have stimulated considerable study in the field, and a number of case-control studies have been performed to investigate the contribution of maternal polymorphisms of genes involved in one-carbon metabolism as risk things for having a kid with DS (reviewed in [14]).Airments of one-carbon metabolism, as a result of the presence of polymorphic genes, might be maternal threat variables for the birth of a youngster with DS [11], and subsequent in vitro research revealed that folate deficiency induces chromosome 21 aneuploidy [12,13].Airments of one-carbon metabolism, on account of the presence of polymorphic genes, may be maternal threat factors for the birth of a youngster with DS [11], and subsequent in vitro research revealed that folate deficiency induces chromosome 21 aneuploidy [12,13]. These papers have stimulated considerable investigation inside the field, and many case-control studies have already been performed to investigate the contribution of maternal polymorphisms of genes involved in one-carbon metabolism as risk elements for obtaining a youngster with DS (reviewed in [14]). Unfortunately, the majority of these research have been carried out in compact cohorts of much less than, or about, one hundred case mothers each, and were typically underpowered to evaluate the independent contribution of each studied polymorphism towards the maternal risk for trisomy 21 within the offspring [14]. Meta-analyses of published information have been performed to overcome the limits of compact case-control cohorts, revealing that each the methylenetetrahydrofolate reductase (MTHFR c.677C>T) along with the methionine synthase reductase (MTRRNutrients 2013,c.66A>G) polymorphisms (both genes are involved in folate metabolism) could possibly represent independent maternal danger factors for the birth of a child with DS [15?7]. Other polymorphic genes participating in one-carbon metabolism happen to be studied much less extensively than the two earlier ones, and benefits are nevertheless borderline or inconclusive for most of them [15]. In 2000, Chango and coworkers [18] identified a frequent c.80A>G polymorphism within the gene coding for RFC-1 (SLC19A1 gene, commonly called RFC-1 gene), that was associated with improved plasma homocysteine (hcy) and decreased folate levels in combination using the MTHFR 677C>T a single [18]. In 2006, we 1st recommended a contribution from the RFC-1 80A>G polymorphism to the maternal risk of birth of a child with DS, observing association with maternal risk in mixture with MTHFR 677C>T or MTHFR 1298A>C polymorphisms [19]. Subsequent research have already been conflicting with some authors observing an independent association in the RFC-1 80A>G polymorphism together with the maternal threat of DS in the offspring [20,21] or even more complicated interactions among RFC-1 and other polymorphisms in genes involved in one-carbon metabolism [22?4], and other individuals failing to locate any association of RFC-1 80A>G alone or combined [25?7]. Moreover, the RFC-1 80A>G polymorphism has been associated with decreased red cell folate concentrations among women [28], and with reduced serum folate concentrations in mothers of DS folks (MDS) [29]. In addition, the RFC-1 gene maps to chromosome 21, is over-expressed in DS individuals, and could possibly contribute to impaired a single carbon metabolism and to the severity on the DS phenotype [30,31]. Within this regard, maternal RFC-1 polymorphisms have been linked with congenital heart disease inside the DS youngster [32]. A meta-analysis [15] of four genetic association studies [19,20,22,25], for a total of 354 MDS and 644 control mothers, was performed in 2009 to address the rol.