Null association of maternal MTHFR A1298C polymorphism with Down syndrome pregnancy: an updated meta-analysis

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

Role of MTHFR A1298C gene polymorphism in the etiology of prostate cancer: a systematic review and updated meta-analysis

Methylenetetrahydrofolate reductase [MTHFR] is an important enzyme of folate/homocysteine pathway and is essential for synthesis, repair and methylation of DNA. Various studies have performed to evaluate the role of MTHFR A1298C gene polymorphism to the risk of prostate cancer and the results were inconclusive and inconsistent. A meta-analysis of published case-control studies, up to December 2014, was performed to investigate the association between MTHFR A1298C gene polymorphism and the susceptibility of prostate cancer. PubMed, Science direct, Springer link and Google scholar databases were searched for case-control studies and crude odds ratios [ORs] with 95% confidence intervals [CIs] were calculated to estimate the strength of association. The analyses were conducted with Open Meta-Analyst and MIX softwares. Total thirteen case-control studies with 4673 prostate cancer patients and 6982 controls were included in this meta-analysis. No associations were observed between MTHFR A1298C gene polymorphism and prostate cancer in any genetic model [allele contrast [C vs. A]: OR = 1.01; 95% CI: 0.91-1.13; p= 0.73; dominant model [CC + AC vs. AA]: OR= 0.98, 95% CI= 0.91-1.06, p= 0.73; homozygote model [CC vs. AA]: OR = 0.96, 95% CI= 0.83-1.10, p= 0.55; co-dominant model [AC vs. AA]: OR= 0.98, 95% CI= 0.91-1.07, p= 0.76; and recessive model [CC vs. AC + AA]: OR =0.96, 95% CI= 0.84-1.10, p= 0.61]. Moreover, when the data were stratified on the basis of ethnicity no significant associations were observed. The results of the present meta-analysis suggest that the MTHFR A1298C gene polymorphism has no effect on the etiology of prostate cancer