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

Abstract

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with thrombophilia due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Several case-control studies were investigated MTHFR C677T polymorphism as risk for recurrent pregnancy loss (RPL). These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of RPL whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies published from Asian population relating the C677T polymorphism to the risk of RPL was conducted. The following electronic databases were searched without language restrictions: PubMed, Google Scholars, Elsevier and Springer Link up to December, 2015. Meta-analysis was performed using MetaAnalyst and Mix version 1.7. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased RPL risk in Asian population using all five genetic models (for T vs. C: OR 1.35, 95 % CI 1.09-1.68, p = 0.009; for TT ? CT vs. CC: OR 1.44, 95 % CI 1.14-1.82, p = 0.006; for CT vs. CC: OR 1.39, 95 % CI 1.07-1.8, p = 0.01; for TT vs. CC: OR 1.79, 95 % CI 1.23.2.6, p = 0.007; for TT vs. CT ? CC: OR 1.61, 95 % CI 1.02-2.56, p = 0.04). In conclusion, this meta-analysis demonstrates a strong association between the MTHFR C677T variant and RPL in Asian population and raising the importance of the use of folate in its treatment and prevention.

MTHFR3′-untranslated region polymorphisms contribute to recurrent pregnancy loss risk and alterations in peripheral natural killer cell proportions

“…To our knowledge, this is the first study to provide evidence linking 3′-UTR polymorphisms of MTHFR with RPL. Combined with previous findings linking MTHFR polymorphisms with increased RPL susceptibility [ 15 16 17 ], our data implicate genetic variation in the 3′-UTR, further supporting the role of MTHFR in RPL.…”

“…Previous studies have reported haplotype analysis of MTHFR 677C>T and 1298A>C [ 6 11 12 14 16 17 ], but the single nucleotide polymorphisms (SNPs) present in the 3′-UTR have not been analyzed. These additional SNPs may alter MTHFR expression or function, as was found with MTHFR 677C>T SNPs with regard to RPL.…”

“…The MTHFR 677T allele was closely correlated with decreased MTHFR activity, resulting in folate deficiency and increased plasma Hcy levels [ 11 ]. Furthermore, the 677T allele was determined to be a potential genetic risk factor for increased RPL susceptibility in recent meta-analyses [ 17 ]. Although an association between RPL and genetic variation of the 3′-untranslated region (UTR) of MTHFR has been reported [ 18 ], such variants and their associations with RPL have not been studied in detail [ 19 ].…”

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Recurrent Pregnancy Loss: a Case-Control Study

“…Results from several meta-analyses that have examined the possibility of an association between MTHFR polymorphisms and the risk of RPL are variable ( 29 30 31 32 33 34 35 36 37 ). Data from a recent, large meta-analysis indicated that maternal and paternal MTHFR C677T and A1298C polymorphisms were associated with RPL.…”

Building a molecular typing protocol for rs1801133 based on real-time PCR HRM technique

“…It is a homologous  Building a molecular typing protocol for rs1801133 based on real-time PCR HRM technique form of the cysteine amino acid but differs from the -CH2 moiety [6]. High levels of homocysteine in the blood are often associated with increased cardiovascular risk, neurological diseases, miscarriage, cancer, infertility in different populations and races [7][8][9][10][11]. In addition, this SNP is associated with the prognosis of treatment with anticancer drugs.…”