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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

Forest plots of association between MTHFR C677T polymorphism and NSCLP risk.A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC and D; TT vs. CT+CC.
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Figure 2: Forest plots of association between MTHFR C677T polymorphism and NSCLP risk.A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC and D; TT vs. CT+CC.

Mentions: Overall, for maternal MTHFR C677T polymorphism,there were significant heterogeneityfor heterozygote comparison (CT versusCC: Ph=0.008) and dominant model comparison(CT+TT versus CC: Ph=0.004), but not forthe homozygote comparison (TT versus CC:Ph=0.076) and the recessive model comparison(TT versus CT+CC: Ph=0.102) (Table 3,Fig 2). Thus, we performed subgroup analysisstratified by source of controls and ethnicityto assess the cause of heterogeneity. Resultssuggested that ethnicity and source of controlswere contributing to substantial heterogeneity.In A1298C polymorphism studies, there wereno significant heterogeneity for all comparisons(all Ph>0.05, Table 4, Fig 3).


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)

Forest plots of association between MTHFR C677T polymorphism and NSCLP risk.A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC and D; TT vs. CT+CC.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Forest plots of association between MTHFR C677T polymorphism and NSCLP risk.A; TT vs. CC, B; CT vs. CC, C; CT+TT vs. CC and D; TT vs. CT+CC.
Mentions: Overall, for maternal MTHFR C677T polymorphism,there were significant heterogeneityfor heterozygote comparison (CT versusCC: Ph=0.008) and dominant model comparison(CT+TT versus CC: Ph=0.004), but not forthe homozygote comparison (TT versus CC:Ph=0.076) and the recessive model comparison(TT versus CT+CC: Ph=0.102) (Table 3,Fig 2). Thus, we performed subgroup analysisstratified by source of controls and ethnicityto assess the cause of heterogeneity. Resultssuggested that ethnicity and source of controlswere contributing to substantial heterogeneity.In A1298C polymorphism studies, there wereno significant heterogeneity for all comparisons(all Ph>0.05, Table 4, Fig 3).

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