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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

Forest plots showing the association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS in overall population. GG/AG versus AA (a), GG versus AG/AA (b), AG versus AA (c), and GG versus AA (d) comparisons are illustrated. The squares represent odds ratios (ORs) and lines represent confidence intervals (95% CI). DSM: Down syndrome mothers; CM: control mothers.
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fig2: Forest plots showing the association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS in overall population. GG/AG versus AA (a), GG versus AG/AA (b), AG versus AA (c), and GG versus AA (d) comparisons are illustrated. The squares represent odds ratios (ORs) and lines represent confidence intervals (95% CI). DSM: Down syndrome mothers; CM: control mothers.

Mentions: We conducted meta-analysis based on 13 case-control studies [25–32, 34–37, 39], including 1,486 DSM and 2,163 CM. Overall, there was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS in all genetic models (Table 2 and Figure 2), except in the allelic comparison (G versus A). However, there was significant heterogeneity among the studies (Table 2).


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)

Forest plots showing the association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS in overall population. GG/AG versus AA (a), GG versus AG/AA (b), AG versus AA (c), and GG versus AA (d) comparisons are illustrated. The squares represent odds ratios (ORs) and lines represent confidence intervals (95% CI). DSM: Down syndrome mothers; CM: control mothers.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Forest plots showing the association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS in overall population. GG/AG versus AA (a), GG versus AG/AA (b), AG versus AA (c), and GG versus AA (d) comparisons are illustrated. The squares represent odds ratios (ORs) and lines represent confidence intervals (95% CI). DSM: Down syndrome mothers; CM: control mothers.
Mentions: We conducted meta-analysis based on 13 case-control studies [25–32, 34–37, 39], including 1,486 DSM and 2,163 CM. Overall, there was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS in all genetic models (Table 2 and Figure 2), except in the allelic comparison (G versus A). However, there was significant heterogeneity among the studies (Table 2).

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