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Null association of maternal <i>MTHFR</i> A1298C polymorphism with Down syndrome pregnancy: An updated meta-analysis

Vandana Rai
Upendra Yadav
Pradeep Kumar


Background: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate/homocysteine pathway and is essential for DNA synthesis and methylation. MTHFR gene polymorphisms have been reported as risk factors for congenital defects and several metabolic and neurological disorders. Several studies have investigated an association between maternal MTHFR A1298C polymorphism and Down syndrome (DS) child. However, results have been inconclusive.

Aim: A meta-analysis of published case–control studies up to December, 2015 was performed to investigate this association.

Methods: Electronic databases were searched for case–control studies and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Total twenty-one case–control studies with 2004 cases and 2523 controls were included in the present meta-analysis.

Results: Results of meta-analysis showed a significant association between maternal A1298C polymorphism and DS pregnancy with homozygote model (CC vs. AA: OR= 1.26, 95% CI= 1.01–1.58, p=0.04), but no such association was found in any other genetic models (C vs. A: OR =1.07, 95% CI= 0.93–1.23, p=0.32; CC + AC vs. AA: OR =1.08, 95% CI= 0.96– 1.23, p=0.18; CC vs. AC+ AA: OR = 1.11, 95% CI= 0.90–1.36, p=0.30; AC vs. AA: OR =1.06, 95% CI= 0.93–1.21, p= 0.34).

Conclusion: Subgroup and sensitivity analysis results showed that this polymorphism is a risk factor for DS pregnancy in Asian populations but not in Caucasian population as well as in overall meta-analysis.

Keywords: Down syndrome; Methylenetetrahydrofolate reductase; MTHFR; A1298C; Homocysteine; Meta-analysis; Folate

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eISSN: 1110-8630