“Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis”

Abstract

Epidemiological studies have evaluated the association between maternal methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms and risk of neural tube defects (NTDs) in offspring. However, the results from the published studies on the association between these three polymorphisms and NTD risk are conflicting. To derive a clearer picture of association between these three maternal polymorphisms and risk of NTD, we performed meta-analysis. A comprehensive search was conducted to identify all case-control studies of maternal MTHFR and MTRR polymorphisms and NTD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that maternal MTHFR C677T polymorphism (OR(TvsC) =1.20; 95% CI = 1.13-1.28) and MTRR A66G polymorphism (OR(GvsA) = 1.21; 95% CI = 0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (OR(CvsA) = 0.91; 95% CI = 0.78-1.07) was not associated with NTD risk. However, in stratified analysis by geographical regions, we found that the maternal C677T polymorphism was significantly associated with the risk of NTD in Asian (OR(TvsC) = 1.43; 95% CI: 1.05-1.94), European (OR(TvsC) = 1.13; 95% CI: 1.04-1.24) and American (OR(TvsC) = 1.26; 95% CI: 1.13-1.41) populations. In conclusion, present meta-analysis supports that the maternal MTHFR C677T and MTRR A66G are polymorphisms contributory to risk for NTD.

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

“…Because of the large sample sizes, metaanalysis has more statistical power than a single study to obtained reliable result. Several large-scale meta-analyses combining data from multiple studies have been published investigating the association between MTHFR C677T polymorphism and various disease/disorders such as- Down syndrome [66], Neural Tube defects [67], cleft lip with/without palate [68], congenital heart defects [69], stroke [70], diabetes mellitus [71], Alzheimers disease [72], schizophrenia [73] and cancer [74].…”

Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies

“…The prevalence of the MTHFR 677TT genotype varies across ethnic groups and regions, ranging from ,2% in West African and African American populations (8,9) to .35% in some populations such as the northern Chinese and individuals of Mexican descent (8)(9)(10). Meta-analyses reported that mothers or infants with the TT genotype have significantly greater odds of a neural tube defect-affected pregnancy than do those with the CC genotype (11)(12)(13).…”

Developmental Origins of Disease - Crisis Precipitates Change

“…Other studies later demonstrated similar independent associations between specific maternal genes and offspring phenotype without any transmission of the particular gene [168][169][170][171][172][173][174][175][176][177][178][179]. It was shown that maternal mutations of relevant genes involved in folate metabolism are associated with an increased risk for neural tube or congenital heart defects [170][171][172]. Similar findings were demonstrated for maternal polymorphisms involved in glucose metabolism [173].…”