Association between MTHFR polymorphisms and orofacial clefts risk: A meta‐analysis

Abstract

Electronic literature searches of the PubMed, EmBase, and Medline databases were performed up to October 31, 2011. Fixed-effects or random-effects models were used to calculate the pooled odds ratios (ORs) for two genetic comparisons (heterozygous mutation vs. wild type, homozygous mutation vs. wild type). RESULTS A total of 18 studies were ultimately identified. The pooled results revealed no statistical association between infant and maternal C677T and A1298C variants and risk of cleft lip with or without palate (CL/P) or cleft palate only (CPO), except for the maternal 677TT genotype for CL/P, the OR was 1.32 (95% confidence interval [CI], 1.06-1.63) as compared to the normal 677CC genotype. In the subgroup analyses on CL/P data based on ethnicity and source of control subjects, almost all of the results were replicated as nonsignificant associations in both examined polymorphisms, whereas the pooled risk estimate calculated for maternal 677TT genotype in the white population remained statistically significant, with an OR of 1.36 (95% CI, 1.05-1.76). CONCLUSIONS This meta-analysis suggests that maternal MTHFR 677TT genotype might increase the risk of having a CL/P offspring in the white population. However, these findings remain to be confirmed by additional investigations.

Association between MTHFR C677T and A1298C Polymorphisms and NSCL/P Risk in Asians: A Meta-Analysis

“…According to Verkleij-Hagoort et al(2007) [19] and Johnson and Little (2008) [20], no significant associations between MTHFR C677T and A1298C polymorphisms and NSCL/P were acquired. The pooled results of Luo Y et al (2012) [17] indicated that maternal MTHFR 677TT genotype was related to increased risk of having a NSCL/P offspring. The more recently meta-analysis conducted by Pan Y et al (2012) [18] showed that MTHFR C677T polymorphism contributed to elevated risk of NSCL/P among Asians.…”

“…Since then, a great number of studies have been conducted, but the results were inconsistent [14]–[16]. In order to elucidate the role of MTHFR C677T and A1298C polymorphisms in NSCL/P, several meta-analyses were performed [17]–[20], but the relationships especially among Asian subjects remained unclear. Recently, some new case-control studies with large sample size have been published [21]–[23].…”

MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

“…Interestingly, rs1801133 (C677T) polymorphism in MTHFR is the most extensively investigated in NSCL/P in both affected patients and their parents. Although the association between rs1801133 and oral cleft risk is controversial, with some studies showing significant association while others rebutting it (Luo et al, ; Butali et al, ), the studies with the Brazilian population refuted the association of this polymorphism with both maternal and fetal risk for NSCL/P (Gaspar et al, ; Brandalize et al, ; Bufalino et al, ). Revaluating our published data (Bufalino et al, ), we found a linkage equilibrium between rs1801133 and rs2274976 (D′ = 0.10), revealing that the genotypes present at those loci are independent.…”

A family-based study of gene variants and maternal folate and choline in neuroblastoma: a report from the Children’s Oncology Group

“…MTHFR 667C>T (rs1801133), one of the most highly studied variants with known functional effects on one-carbon metabolism, [37–39] had a null offspring association (RR: 0.99, 95% CI: 0.84–1.19) and a weak maternal association (RR: 1.16, 95% CI: 0.97–1.38). Two previous studies of candidate SNPs from folate-related genes identified SLC19A1 80G>A (rs1051266) as positively associated with neuroblastoma in Brazil [40, 41].…”