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Disease Markers
Volume 28, Issue 5, Pages 293-298

Functional Inference of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Enzyme Stability as a Potential Risk Factor for Down Syndrome in Croatia

Jadranka Vraneković,1 Ivana Babić Božović,1 Nada Starčević Čizmarević,1 Alena Buretić-Tomljanović,1 Smiljana Ristić,1 Oleg Petrović,2 Miljenko Kapović,1 and Bojana Brajenović-Milić1

1Department of Biology and Medical genetics, School of Medicine, University of Rijeka, Rijeka, Croatia
2Department of Obstetrics and Gynecology, Rijeka University Hospital, Rijeka, Croatia

Received 25 June 2010; Accepted 25 June 2010

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 χ2 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.