Analysis of seven maternal polymorphisms of genes involved in homocysteine/folate metabolism and risk of Down syndrome offspring.

Abstract

PURPOSE We present a case-control study of seven polymorphisms of six genes involved in homocysteine/folate pathway as risk factors for Down syndrome. Gene-gene/allele-allele interactions, haplotype analysis and the association with age at conception were also evaluated. METHODS We investigated 94 Down syndrome-mothers and 264 control-women from Campania, Italy. RESULTS Increased risk of Down syndrome was associated with the methylenetetrahydrofolate reductase (MTHFR) 1298C allele (OR 1.46; 95% CI 1.02-2.10), the MTHFR 1298CC genotype (OR 2.29; 95% CI 1.06-4.96), the reduced-folate-carrier1 (RFC1) 80G allele (1.48; 95% CI 1.05-2.10) and the RFC1 80 GG genotype (OR 2.05; 95% CI 1.03-4.07). Significant associations were found between maternal age at conception > or = 34 years and either the MTHFR 1298C or the RFC 180G alleles. Positive interactions were found for the following genotype-pairs: MTHFR 677TT and 1298CC/CA, 1298CC/CA and RFC1 80 GG/GA, RFC1 80 GG and methylenetetrahydrofolate-dehydrogenase 1958 AA. The 677-1298 T-C haplotype at the MTHFR locus was also a risk factor for Down syndrome (P = 0.0022). The methionine-synthase-reductase A66G, the methionine-synthase A2756G and the cystathionine-beta-synthase 844ins68 polymorphisms were not associated with increased risk of Down syndrome. CONCLUSION These results point to a role of maternal polymorphisms of homocysteine/folate pathway as risk factors for Down syndrome.

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@article{Scala2006AnalysisOS, title={Analysis of seven maternal polymorphisms of genes involved in homocysteine/folate metabolism and risk of Down syndrome offspring.}, author={Iris Scala and Barbara Granese and Maria Sellitto and Serena Salom{\`e} and Annalidia Sammartino and Antonio Pepe and Pierpaolo Mastroiacovo and Gianfranco Sebastio and Generoso Andria}, journal={Genetics in medicine : official journal of the American College of Medical Genetics}, year={2006}, volume={8 7}, pages={409-16} }