| Objective:Cleft Lip and Palate(CLP) are a common congenital malformation of birth defects,a higher prevalence,ranking second in congenital diseases,and its pathogenesy remains unclear.Previous studies showed that the etiology of the CLP was closely related with genetic and environmental factors. So far, the relevant environmental factors and virulence genes have been found unceasingly, but their specific relevance and pathogenic mechanism remain unclear. Related disease genes are mainly:TGFα, TGFβ3, PVRL1, BCL3, IRF6, MTHFR, MSX1, PAX9, RARA, etc; relevant environmental factors are: physical damages, chemical factors, biological factors, fetal internal environment and the individual factors of the mother.Previous studies have found that the formation of folic acid in the embryonic ectoderm of the maxillary protrusion, and the Globular axon plays an important role in the integration process,so folic acid metabolism is closely related with the formation of cleft lip and palate.5,10-methylenetetrahydrofolate reductase (MTHFR),the gene encoding 5,10-methylenetetrahydrofolate reductase,is a key enzyme in folate metabolism, it catalyzed 5,10-methylenetetrahydrofolate to make it revert to the 5-methylenete-trahydrofolate, becoming the main activity of folic acid in the body form. Studies have shown that the gene C677T polymorphism and non-syndrome cleft lip and palate (NSCL/P) may be related, but foreign and domestic research results are quite different, and there is a lack of relevant reserch on the effect that intervention factors with folic acid during pregnancy on the morbidity of NSCL/P.①To investigate the MTHFR gene C677T polymorphism on patients with non-syndromic cleft lip and palate of the Han population in Henan;②The relationship between folate supplementation during pregnancy and family history factors to the incidence of non-syndromic cleft lip and palate;③The co-pathogenicity of MTHFR gene C677T locus and folic acid supplementation on NSCL/P patients.Materials and methods:①Selected 110 cases of patients with non-syndromic cleft lip and palate who were treated at the First Affiliated Hospital of Zhengzhou University or the First People's Hospital of Zhengzhou City from September 2008 to March 2010.②Detected by PCR-RFLPs in the peripheral blood of 110 patients and 40 healthy control group MTHFR C677T locus to compare allele frequency differences.③Whether the combination of folic acid supplementation during pregnancy and family history factors to the NSCL/P that was done by statisticallyχ2 test, and correlation analysis to determine gene-environment interaction exists between them.Results:1.Case group and control group C677T genotype and allele frequency comparison, the differences were significant (χ2= 9.55, P<0.01), TT genotype in case group accounted for 20%, CT genotype 62.5%; control group The TT genotype accounted for 15%, CT genotype 32.5%; patient group accounted for 51.36% with T allele was significantly higher than the 31.25%, is about 1.64 times than the control group;2. Cases of patients with a family history of genotype TT and T allele frequency are higher than patients without family history (χ2=10.93,P<0.05),statistically significant differences;3.Genotypes of various types of cleft lip and palate compared with the control group:cleft lip group and control groupχ2=4.802,P=0.028<0.05,statistically significant; cleft palate only group and control groupχ2=9.068, P<0.05, statistically significance;cleft lip and palate group with control group,χ2=6.927,P<0.05, statistically significant;4.Comparison of cases and controls whether folic acid supplementation during pregnancy, Folic acid group, NSCL/P incidence rate of 65.22%, not to add folic acid group, NSCL/P incidence rate of 80.25%.higher than it about 1.23 times,χ2= 4.304, P<0.05,γ=-0.169, showing a negative correlation.5.To CC genotype and not folic acid supplementation during pregnancy as a reference, the CT, TT genotype and folate deficiency has pathogenic interaction (P <0.05), risk of NSCL/P, respectively, the risk of folate supplementation for the CC genotype and the 10.200-folds (95% CI:1.612～64.556) and 8.500-folds (95% CI: 0.971-74.424).Conclusions:1. MTHFR gene C677T mutation and the incidence of NSCL/P in Henan Han population were associated,and mutant allele T can increase the risk of the NSCL/P;2.Folate supplementation during pregnancy could significantly reduced the risk of the NSCL/P,showing a negative correlation;3.Family history of the NSCL/P has some relevance to its pathogenesis; Cleft lip, Cleft palate only and CLP were associated with MTHFR gene C677T mutation;4.There were interactive pathogenic roles between the CT, TT genotype and folate deficiency. |
PDF Full Text Request