Genetic Polymorphisms Involved in Folate Metabolism and Maternal Risk for Down Syndrome: A Meta-Analysis

Author:

Balduino Victorino Daniella1,de Godoy Moacir Fernandes2,Goloni-Bertollo Eny Maria1,Pavarino Érika Cristina1

Affiliation:

1. Unidade de Pesquisa em Genética e Biologia Molecular (UPGEM), Faculdade de Medicina de São José do Rio Preto (FAMERP), Avenida Brigadeiro Faria Lima No. 5416, Bloco U-6, 15090-000 São José do Rio Preto, SP, Brazil

2. Núcleo Transdisciplinar para Estudo do Caos e da Complexidade (NUTECC), Faculdade de Medicina de São José do Rio Preto (FAMERP), 15090-000 São José do Rio Preto, SP, Brazil

Abstract

Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated usingQ-test andI2statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg’s and Egger’s tests. A total of 17 case-controls studies were included. There was evidence for an association between theMTRRc.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygoteMTHFD11958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, consideringMTRc.2756A>G (rs1805087),TC2c.776C>G (rs1801198), andCBSc.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that theMTRRc.66A>G (rs1801394) polymorphism andMTHFD1c.1958G>A (rs2236225) were associated with increased maternal risk for DS.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Hindawi Limited

Subject

Biochemistry, medical,Clinical Biochemistry,Genetics,Molecular Biology,General Medicine

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