Methylenetetrahydrofolate reductase C677T polymorphism is not associated with the risk of nonsyndromic cleft lip/palate: An updated meta-analysis

Abstract

Both genetic and environmental factors affect the risk of orofacial clefts. The present meta-analysis aimed to evaluate the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of nonsyndromic cleft lip/palate (NSCL/P) in cases-control studies. The PubMed/Medline, Scopus, Web of Science, and Cochrane Library databases were searched up to April 2019 with no restrictions. The odds ratios (ORs) and 95% confidence intervals (CIs) in all analyses were calculated by Review Manager 5.3 software. The funnel plot analysis was carried out by the Comprehensive Meta-Analysis version 2.0 software. Subgroup analysis, meta-regression, and sensitivity analysis were performed for the pooled analyses. Thirty-one studies reviewed in this meta-analysis included 4710 NSCL/P patients and 7271 controls. There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility related to allelic model (OR = 1.04; P = 0.49), homozygote model (OR = 1.11; P = 0.35), heterozygote model (OR = 0.99; P = 0.91), dominant model (OR = 1.00; P = 0.96), or recessive model (OR = 1.08; P = 0.23). There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility based on the ethnicity or the source of cases. There was a significant linear relationship between the year of publication and log ORs for the allele model. The results of the present meta-analysis failed to show an association between MTHFR C677T polymorphism and NSCL/P susceptibility. The subgroup analyses based on the ethnicity and the source of cases further confirmed this result.

Figure 1

Flowchart of the study.

Figure 2

Random-effect forest plot of allele model (T vs. C) for the association between the NSCL/P risk and MTHFR C677T polymorphism.

Figure 3

Random-effect forest plot of homozygote model (TT vs. CC) for the association between the NSCL/P risk and MTHFR C677T polymorphism.

Figure 4

Random-effect forest plot of heterozygote model (CT vs. CC) for the association between the NSCL/P risk and MTHFR C677T polymorphism.

Figure 5

Random-effect forest plot of dominant model (TT + CT vs. CC) for the association between the NSCL/P risk and MTHFR C677T polymorphism.

Figure 6

Random-effect forest plot of recessive model (TT vs. CC + CT) for the association between the NSCL/P risk and MTHFR C677T polymorphism.

Figure 7

Fixed-effect meta-regression of log odds ratio versus publication year for (A) allele model, (B) homozygote model, (C) heterozygote model, (D) dominant model, and (E) recessive model.

Figure 8

Fixed-effect meta-regression of log odds ratio versus number of individuals for (A) allele model, (B) homozygote model, (C) heterozygote model, (D) dominant model, and (E) recessive model.

Figure 9

Funnel plot of (A) allele model, (B) homozygote model, (C) heterozygote model, (D) dominant model, and (E) recessive model for the association between the NSCL/P risk and MTHFR C677T polymorphism (fixed-effects model).