title: Functional inference of methylenetetrahydrofolate reductase gene polymorphisms on enzyme stability as a potential risk factor for Down syndrome in Croatia.
abstract: Understanding the biochemical structure and function of the methylenetetrahydrofolate reductase gene (MTHFR) provides new evidence in elucidating the risk of having a child with Down syndrome (DS) in association with two common MTHFR polymorphisms, C677T and A1298C. The aim of this study was to evaluate the risk for DS according to the presence of MTHFR C677T and A1298C polymorphisms as well as the stability of the enzyme configuration. This study included mothers from Croatia with a liveborn DS child (n=102) or DS pregnancy (n=9) and mothers with a healthy child (n=141). MTHFR C677T and A1298C polymorphisms were assessed by PCR-RFLP. Allele/genotype frequencies differences were determined using chi square test. Odds ratio and the 95% confidence intervals were calculated to evaluate the effects of different alleles/genotypes. No statistically significant differences were found between the frequencies of allele/genotype or genotype combinations of the MTHFR C677T and A1298C polymorphisms in the case and the control groups. Additionally, the observed frequencies of the stable (677CC/1298AA, 677CC/1298AC, 677CC/1298CC) and unstable (677CT/1298AA, 677CT/1298AC, 677TT/1298AA) enzyme configurations were not significantly different. We found no evidence to support the possibility that MTHFR polymorphisms and the stability of the enzyme configurations were associated with risk of having a child with DS in Croatian population.
authors.affiliation: Department of Biology and Medical genetics, University of Rijeka, Croatia.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Vraneković
authors.forename: Ivana
authors.initials: I
authors.lastname: Babić Bozović
authors.forename: Nada
authors.initials: N
authors.lastname: Starcević Cizmarević
authors.forename: Alena
authors.initials: A
authors.lastname: Buretić-Tomljanović
authors.forename: Smiljana
authors.initials: S
authors.lastname: Ristić
authors.forename: Oleg
authors.initials: O
authors.lastname: Petrović
authors.forename: Miljenko
authors.initials: M
authors.lastname: Kapović
authors.forename: Bojana
authors.initials: B
authors.lastname: Brajenović-Milić
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004314:Down Syndrome / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D004795:Enzyme Stability / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000737:chemistry* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D012307:Risk Factors; D055815:Young Adult
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)