Association between MTHFR polymorphisms and orofacial clefts risk: a meta-analysis.
ABSTRACT BACKGROUND The roles of C677T and A1298C polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene in orofacial clefts (OFCs) risk have been substantially explored, but the results remain conflicting. To address this gap, we conducted a meta-analysis involving all eligible studies. METHODS: 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.
SourceAvailable from: Farnaz Mohajertehran[Show abstract] [Hide abstract]
ABSTRACT: Abstract Background: Non-syndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital abnormalities of the orofacial region with a multifactorial etiology. The present study aimed to investigate the association of two common polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene (c.677C>T and c.1298A>C) with the occurrence of nsCL/P in an Iranian population. Methods: Forty-five nsCL/P patients, 43 mothers of patients, and 101 unrelated controls participated in the present study. Analysis of c.677C>T and c.1298A>C polymorphisms in MTHFR gene was conducted using polymerase chain reaction and restriction enzyme digestions. Results: There was no statistical difference in genotype and allele frequencies for c.677C>T variants between patients or their mothers and the control group. However, differences in the frequencies of alleles and genotypes of c.1298A>C polymorphism were statistically significant between patients and control group (P=0.01 for alleles and P=0.005 for genotypes). The odds ratios (OR) for the CC versus AA homozygotes were 6.1 (95% CI 1.8-20.5) and 4.2 (95% CI 1.1-15.4), in patients and mothers, respectively. Conclusions: We found no association between genetic polymorphism of MTHFR c.677C>T and the risk of nsCL/P in the population studied. Yet the results suggested that c.1298A>C polymorphism of MTHFR gene may be a risk factor for the occurrence of nsCL/P in the Iranian population. Keywords: MTHFR, Folic acid, Methylenetetrahydrofolate reductase, Cleft Lip, Cleft palate, Non-syndromic cleft
[Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to examine the presence and extent of publication bias and small-study effects in meta-analyses (MAs) investigating pediatric dentistry-related subjects. Following a literature search, 46 MAs including 882 studies were analyzed qualitatively. Of these, 39 provided enough data to be re-analyzed. Publication bias was assessed with the following methods: contour-enhanced funnel plots, Begg and Mazumdar's rank correlation and Egger's linear regression tests, Rosenthal's failsafe N, and Duval and Tweedie's "trim and fill" procedure. Only a few MAs adequately assessed the existence and effect of publication bias. Inspection of the funnel plots indicated asymmetry, which was confirmed by Begg-Mazumdar's test in 18% and by Egger's test in 33% of the MAs. According to Rosenthal's criterion, 80% of the MAs were robust, while adjusted effects with unpublished studies differed from little to great from the unadjusted ones. Pooling of the Egger's intercepts indicated that evidence of asymmetry was found in the pediatric dental literature, which was accentuated in dental journals and in diagnostic MAs. Since indications of small-study effects and publication bias in pediatric dentistry were found, the influence of small or missing trials on estimated treatment effects should be routinely assessed in future MAs. Copyright © 2015 Elsevier Inc. All rights reserved.Journal of Evidence Based Dental Practice 03/2015; 15(1):8-24. DOI:10.1016/j.jebdp.2014.09.001
[Show abstract] [Hide abstract]
ABSTRACT: Congenital left-sided lesions (LSLs) are serious, heritable malformations of the heart. However, little is known about the genetic causes of LSLs. This study was undertaken to identify common variants acting through the genotype of the affected individual (i.e. case) or the mother (e.g. via an in utero effect) that influence the risk of LSLs. A genome-wide association study (GWAS) was performed using data from 377 LSL case-parent triads, with follow-up studies in an independent sample of 224 triads and analysis of the combined data. Associations with both the case and maternal genotypes were assessed using log-linear analyses under an additive model. An association between LSLs and the case genotype for one intergenic SNP on chromosome 16 achieved genome-wide significance in the combined data (rs8061121, combined P=4.0x10(-9); relative risk to heterozygote: 2.6, 95% CI 1.9-3.7). In the combined data, there was also suggestive evidence of association between LSLs and the case genotype for a variant in the synaptoporin gene (rs1975649, combined P=3.4x10(-7); relative risk to heterozygote: 1.6, 95% CI 1.4-2.0) and between LSLs and the maternal genotype for an intergenic SNP on chromosome 10 (rs11008222, combined P=6.3x10(-7); relative risk to heterozygote: 1.6, 95% CI 1.4-2.0). This is the first GWAS of LSLs to evaluate associations with both the case and maternal genotypes. The results of this study identify three candidate LSL susceptibility loci, including one that appears to be associated with the risk of LSL via the maternal genotype.Human Molecular Genetics 08/2014; DOI:10.1093/hmg/ddu420 · 6.68 Impact Factor