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Genetic polymorphisms involved in folate metabolism and maternal risk for down syndrome: a meta-analysis.

Balduino Victorino D, de Godoy MF, Goloni-Bertollo EM, Pavarino ÉC - Dis. Markers (2014)

Bottom Line: In the subgroup analysis, increased maternal risk for DS was found in Caucasians.Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.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 the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS.

View Article: PubMed Central - PubMed

Affiliation: 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.

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 using Q-test and I (2) statistic. 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 the MTRR c.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 heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.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 the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS.

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Related in: MedlinePlus

Flow diagram of eligible study selection process and studies excluded, with specification of reasons.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig1: Flow diagram of eligible study selection process and studies excluded, with specification of reasons.

Mentions: The literature search identified 116 potentially relevant studies; of these, 88 were excluded after screening the titles and abstracts. The full-text studies were retrieved for a detailed assessment. Eleven studies were excluded for specified reasons (6 articles with overlapping data of the same population resource, 2 articles with Down syndrome individuals as cases, and 3 articles with insufficient data). Finally, 17 case-control studies [25–41] with a total number of 1,988 DSM and 2,739 CM were included in the MTR c.2756A>G (rs1805087), MTRR c.66A>G (rs1801394), TC2 c.776C>G (rs1801198), CBS c.844ins68, and MTHFD1 c.1958G>A (rs2236225) meta-analysis (Figure 1).


Genetic polymorphisms involved in folate metabolism and maternal risk for down syndrome: a meta-analysis.

Balduino Victorino D, de Godoy MF, Goloni-Bertollo EM, Pavarino ÉC - Dis. Markers (2014)

Flow diagram of eligible study selection process and studies excluded, with specification of reasons.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4269293&req=5

fig1: Flow diagram of eligible study selection process and studies excluded, with specification of reasons.
Mentions: The literature search identified 116 potentially relevant studies; of these, 88 were excluded after screening the titles and abstracts. The full-text studies were retrieved for a detailed assessment. Eleven studies were excluded for specified reasons (6 articles with overlapping data of the same population resource, 2 articles with Down syndrome individuals as cases, and 3 articles with insufficient data). Finally, 17 case-control studies [25–41] with a total number of 1,988 DSM and 2,739 CM were included in the MTR c.2756A>G (rs1805087), MTRR c.66A>G (rs1801394), TC2 c.776C>G (rs1801198), CBS c.844ins68, and MTHFD1 c.1958G>A (rs2236225) meta-analysis (Figure 1).

Bottom Line: In the subgroup analysis, increased maternal risk for DS was found in Caucasians.Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.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 the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS.

View Article: PubMed Central - PubMed

Affiliation: 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.

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 using Q-test and I (2) statistic. 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 the MTRR c.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 heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.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 the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS.

Show MeSH
Related in: MedlinePlus