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Polymorphism in folate metabolic pathway gene as maternal risk factor for down syndrome

Authors:Vandana Rai
Int J Biol Med Res. 2011; 2(4): 1055 – 1060  |  PDF File


Down syndrome (DS) with the prevalence of 1/700 to 800 live births is the most common cause of mental retardation in human. During last two decades, it was repeatedly reported that besides advanced maternal age at conception impairment in maternal folate metabolism and elevated homocysteine are also risk factors for having a DS child. Methionine synthase reductase (MTRR) is the vital enzyme of folate/methionine metabolism cycle and dysfunctional MTRR enzyme lead to higher level of homocysteine and abnormal DNA methylation. Normal DNA methylation at centromeric and pericentromeric regions is responsible for normal segregation of chromosomes. Abnormal methylation of centromeric DNA due to A66G mutation is the main reason behind the trisomy 21. A number of association studies on MTRR, have focused on possible links between the maternal MTRR A66G polymorphism and birth of DS child but no consistent results have been obtained with regard to DS birth hence the aim of present meta-analysis was to examined association between birth of DS child and maternal MTRR A66G polymorphism in published case control reports. The present meta-analysis included total six studies with 623 case samples and 936 control samples. The genotype percentages of AA, AG and GG in cases were 17.17%, 51.2% and 31.62% respectively. Meta-analysis with random effects showed that there was 73.1% heterogeneity between the six studies. The fixed effect pooled OR was 1.34 (95% CI; 1.17 to 1.54) and Cochran Q was 18.57 (df = 5; p=0.0023). The random effect pooled OR was 1.42 (95% CI; 1.05 to 1.92) and Cochran Q was 18.57 (df = 5; p=0.0023). The random effect pooled OR was significant and showed strong association between MTRR A66G maternal genotype and Down syndrome. Meta-analysis was carried out by Meta-disc (version 1.4). The pooled OR of the present meta-analysis reported with 95% certainty that carriers of the 66G allele would have more than 1.42 folds increased risk of having DS child than the women without this allele. MTRR A66G polymorphism needs to be evaluated as a risk factor for Down syndrome in larger sample size.