Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome — meta-analysis |
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Authors: | Igor Medica Ales Maver Goncalo Figueiredo Augusto Borut Peterlin |
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Institution: | (1) Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, 221005 Varanasi, India;(2) Department of Paediatrics, Institute of Medical Sciences, Banaras Hindu University, 221 005 Varanasi, India;(3) Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University, 221 005 Varanasi, India;(4) Department of Zoology, Wolfson College, OX2 6UD Oxford, UK; |
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Abstract: | Folate metabolism deficiency has been related to increased occurrence of maternal non-disjunction resulting in trisomy 21.
Several polymorphisms in genes coding for folate metabolism enzymes have been investigated for association with the maternal
risk of Down syndrome (DS) yielding variable results. We performed a meta-analysis of case-control studies obtained through
the PubMed database. The studies on polymorphisms in the MTHFR, MTRR, MTR, RFC1 and CBS genes were included. The summary OR
demonstrated a statistically significant increased risk of giving birth to a child with DS in mothers carrying the mutant
allele of the MTHFR/C677T gene polymorphism (both genetic models) and in mothers homozygous for the mutant allele of the MTRR/A66G
polymorphism (recessive genetic model). Analyses of other polymorphisms, MTHFR/A1298C, MTR/A2756G, RFC1/A80G, and CBS/844ins68,
resulted in borderline or no statistical significance. In conclusion, our meta-analysis showed the significance of genetic
alterations in the folate metabolism genes in maternal susceptibility to DS offspring. Our results suggest that the importance
of folate supplementation to women in reproductive age in prevention of non-disjunction be revised. Further genetic studies
on a combined effect of multiple folate metabolism genes is recommended. Additionally, more thorough studies on the haplotype
analyses of genes is recommended as well, especially in populations that have not yet been investigated thus far. |
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