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Association between Maternal MTHFR Polymorphisms and Nonsyndromic Cleft Lip with or without Cleft Palate in Offspring, A Meta-Analysis Based on 15 Case-Control Studies.

Pan X, Wang P, Yin X, Liu X, Li D, Li X, Wang Y, Li H, Yu Z - Int J Fertil Steril (2015)

Bottom Line: MTHFR C677T polymorphism is associated with the risk of generating NSCL/P offspring, and being a 677TT homozygote is a risk factor.MTHFR A1298C polymorphism was not associated with generating NSCL/P offspring.However, further work should be performed to confirm these findings.

View Article: PubMed Central - PubMed

Affiliation: College of Public Health, Zhengzhou University, Zhengzhou, China ; Medical College, Henan University of Science and Technology, Luoyang, China.

ABSTRACT

Background: The methylenetetrahydrofolate reductase (MTHFR) is thought to be involved in the development of nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, conflicting results have been obtained when evaluating the association between maternal MTHFR C677T and A1298C polymorphisms and the risk of NSCL/P. In light of this gap, a meta-analysis of all eligible case-control studies was conducted in the present study.

Materials and methods: A total of 15 case-control studies were ultimately identified after a comprehensive literature search and Hardy-Weinberg equilibrium (HWE) examination. Cochrane's Q test and index of heterogeneity (I(2)) indicated no obvious heterogeneity among studies.

Results: Fixed or random-effects models were used to calculate the pooled odds ratios (ORs). The results showed that the TT genotype in mothers increased the likelihood of having NSCL/P offspring 1.25 times (95% CI: 1.047-1.494) more than the CC homozygotes. Meanwhile, maternal TT genotype increased the risk of producing NSCL/P offspring in recessive model (OR=1.325, 95% CI: 1.124-1.562). However, the CT heterozygote and the CT+TT dominant models had no association with NSCL/P offspring compared with the CC wild-type homozygote model. Subgroup analyses based on ethnicity indicated that maternal TT genotype increased the likelihood of having NSCL/P offspring in Whites (OR=1.308, 95% CI: 1.059-1.617) and Asians (OR=1.726, 95% CI: 1.090-2.733) in recessive model. Also, subgroup analyses based on source of control showed that mothers with the 677TT genotype had a significantly increased susceptibility of having NSCL/P children in hospital based population (HB) when compared with CC homozygotes (OR=1.248, 95% CI: 1.024-1.520) and un- der the recessive model (OR=1.324, 95% CI: 1.104-1.588). Furthermore, maternal A1298C polymorphism had no significant association with producing NSCL/P offspring (dominant model OR=0.952, 95% CI: 0.816-1.111, recessive model OR=0.766, 95% CI: 0.567-1.036).

Conclusion: MTHFR C677T polymorphism is associated with the risk of generating NSCL/P offspring, and being a 677TT homozygote is a risk factor. MTHFR A1298C polymorphism was not associated with generating NSCL/P offspring. However, further work should be performed to confirm these findings.

No MeSH data available.


Related in: MedlinePlus

Funnel plots for included studies of MTHFR C677T polymorphism and NSCLP risk. Begg’s funnel plot with pseudo 95%confidence limits. A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC ad D; TT vs. CT+CC.
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Figure 4: Funnel plots for included studies of MTHFR C677T polymorphism and NSCLP risk. Begg’s funnel plot with pseudo 95%confidence limits. A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC ad D; TT vs. CT+CC.

Mentions: No individual study affected the final resultsaccording to sensitivity analyses (data notshown). Funnel plots of all studies revealed noasymmetrical distribution of ORs (Figes4-5),suggesting no significant publication bias inthis study. Begg’s test and Egger’s test providedfurther statistical evidence of no significantpublication bias in this meta-analysis (allp>0.05) (Table 5).


Association between Maternal MTHFR Polymorphisms and Nonsyndromic Cleft Lip with or without Cleft Palate in Offspring, A Meta-Analysis Based on 15 Case-Control Studies.

Pan X, Wang P, Yin X, Liu X, Li D, Li X, Wang Y, Li H, Yu Z - Int J Fertil Steril (2015)

Funnel plots for included studies of MTHFR C677T polymorphism and NSCLP risk. Begg’s funnel plot with pseudo 95%confidence limits. A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC ad D; TT vs. CT+CC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355933&req=5

Figure 4: Funnel plots for included studies of MTHFR C677T polymorphism and NSCLP risk. Begg’s funnel plot with pseudo 95%confidence limits. A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC ad D; TT vs. CT+CC.
Mentions: No individual study affected the final resultsaccording to sensitivity analyses (data notshown). Funnel plots of all studies revealed noasymmetrical distribution of ORs (Figes4-5),suggesting no significant publication bias inthis study. Begg’s test and Egger’s test providedfurther statistical evidence of no significantpublication bias in this meta-analysis (allp>0.05) (Table 5).

Bottom Line: MTHFR C677T polymorphism is associated with the risk of generating NSCL/P offspring, and being a 677TT homozygote is a risk factor.MTHFR A1298C polymorphism was not associated with generating NSCL/P offspring.However, further work should be performed to confirm these findings.

View Article: PubMed Central - PubMed

Affiliation: College of Public Health, Zhengzhou University, Zhengzhou, China ; Medical College, Henan University of Science and Technology, Luoyang, China.

ABSTRACT

Background: The methylenetetrahydrofolate reductase (MTHFR) is thought to be involved in the development of nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, conflicting results have been obtained when evaluating the association between maternal MTHFR C677T and A1298C polymorphisms and the risk of NSCL/P. In light of this gap, a meta-analysis of all eligible case-control studies was conducted in the present study.

Materials and methods: A total of 15 case-control studies were ultimately identified after a comprehensive literature search and Hardy-Weinberg equilibrium (HWE) examination. Cochrane's Q test and index of heterogeneity (I(2)) indicated no obvious heterogeneity among studies.

Results: Fixed or random-effects models were used to calculate the pooled odds ratios (ORs). The results showed that the TT genotype in mothers increased the likelihood of having NSCL/P offspring 1.25 times (95% CI: 1.047-1.494) more than the CC homozygotes. Meanwhile, maternal TT genotype increased the risk of producing NSCL/P offspring in recessive model (OR=1.325, 95% CI: 1.124-1.562). However, the CT heterozygote and the CT+TT dominant models had no association with NSCL/P offspring compared with the CC wild-type homozygote model. Subgroup analyses based on ethnicity indicated that maternal TT genotype increased the likelihood of having NSCL/P offspring in Whites (OR=1.308, 95% CI: 1.059-1.617) and Asians (OR=1.726, 95% CI: 1.090-2.733) in recessive model. Also, subgroup analyses based on source of control showed that mothers with the 677TT genotype had a significantly increased susceptibility of having NSCL/P children in hospital based population (HB) when compared with CC homozygotes (OR=1.248, 95% CI: 1.024-1.520) and un- der the recessive model (OR=1.324, 95% CI: 1.104-1.588). Furthermore, maternal A1298C polymorphism had no significant association with producing NSCL/P offspring (dominant model OR=0.952, 95% CI: 0.816-1.111, recessive model OR=0.766, 95% CI: 0.567-1.036).

Conclusion: MTHFR C677T polymorphism is associated with the risk of generating NSCL/P offspring, and being a 677TT homozygote is a risk factor. MTHFR A1298C polymorphism was not associated with generating NSCL/P offspring. However, further work should be performed to confirm these findings.

No MeSH data available.


Related in: MedlinePlus