MTRR 66A>G polymorphism as maternal risk factor for Down syndrome: a meta-analysis

Abstract

Down syndrome (DS) is the most common cause of mental retardation. Recent reports have investigated possible genetic factors that may increase maternal risk for DS. Methionine synthase reductase (5-methyltetrahydrofolate-homocysteine methyltransferase reductase MTRR) plays an important role in folic acid pathway and a common polymorphism (c.66A>G) has been associated with DS but results were controversial. This meta-analysis summarizes the available data concerning this association. Online major databases were searched to identify case-control studies regarding MTRR 66A>G polymorphism and DS. Crude odds ratios (OR) and 95% confidence intervals (CI) were calculated for maternal risk to have a DS child both using fixed and random effects (RE) models. Eleven articles from six populations were identified, including 1226 DS mothers and 1533 control mothers. Heterogeneity among studies was significant (Q=29.7, DF=10, p=0.001; I(2)=66.3%). The pooled OR in a RE model showed an increase in the risk of having a DS child associated with the G allele (OR 1.23, 95% CI 1.02-1.49). The fixed effect pooled OR was 1.19 (95% CI 1.08-1.31). This meta-analysis indicates that maternal MTRR 66A>G polymorphism is associated with an increased risk of having a DS child.