Association Between Forhead Box E1 Polymorphisms And Nonsyndromic Cleft Lip With Or Without Cleft Palate Risk:A Meta-analysis

Objective Non-syndromic cleft lip and palate(NSCl/P)is one of the most common facial congenital malformations.Many literatures have studied the relationship between FOXE1 polymorphism and NSCL/P,but the results are different.The aim of this study was to systematically evaluate the relationship between FOXE1 gene and NSCL/P by using meta-analysis.Methods According to the principle of PICOS and the principle of PICOS,the key words can be identified as non-syndromic cleft lip and palate,FOXE1 gene and polymorphism.Pub Med,Embase,Cochrane Library,China How Net,Wanfang and other data were searched for articles published before May 2018 on the relationship between FOXE1 gene polymorphism and NSCL/P.Literatures were screened strictly according to inclusion and exclusion criteria.Case-control studies involving FOXE1 gene polymorphism and NSCL/P could obtain full text and original data.Data were extracted from the selected literature by two opposing researchers.Four single nucleotide polymorphisms of FOXE1,including rs3758249,rs4460498,rs1443434 and rs10217225,were analyzed by Stata 12.0.According to heterogeneity,OR,95% CI and P values were calculated by fixed effect model or random effect model.The relationship between Foxe1 polymorphism and NSCL/P was studied by Meta-analysis.Results According to inclusion and exclusion criteria,the database was searched and six studies were included.Eight groups of cases-control group were included in the case group,2477 cases and 2579 cases in the control group.(1)rs3758249 had no significant correlation with CPO.The results of meta-analysis showed that there was no correlation between rs3758249 and CPO.The results of rs3758249 and CL/P study showed that CL/P rs3758249 was a risk factor for Chinese(allele model,A vs G,OR = 1.588 95% CI = 1.223-1.986,P = 0.000;heterozygote model,AG vs GG,OR = 1.949,95% CI = 1.425-2.666,P = 0.000;dominant model,AG + AA vs GG,OR = 1.877,95% CI =1.371-2.535,P = 0.000).For non-Chinese,rs3758249 was a protective factor(CL/P: allele model,A vs G,OR = 0.791 95% CI = 0.678-0.922,P = 0.003;recessive model,AA vs AG + GG,OR = 0.775,95% CI = 0.618-0.972,P = 0.027).(2)There is no significant correlation between rs4460498 and Chinese NSCL/P.But rs4460498 was a protective factor(CL/P: allele model,T vs C,OR = 0.766 95% CI = 0.766 95% CI = 0.678-0.865,P = 0.000;heterozygote model,TC vs CC,OR = 0.708,95% CI = 0.572-0.875,P = 0.001;additive model,TT vs CC,TT vs CC,OR = 0.672,OR = 0.672,95% CI = 0.672,95% CI = 0.672,95% CI = 0.537-0.537-0.820,P = 0.820,P = 0.001;dominadominadominant model,TC OR + TT OR + TT OR = TC OR + TT OR + TT OR OR 95% CI = 0.604-0.798,P = 0.000;implicit model,TT vs TC + CC,OR = 0.758,95% CI = 0.606-0.948,P = 0.015.CPO: heterozygote model,TC vs CC,OR = 0.748,95% CI = 0.560-0.999,P = 0.049.(3)There was no correlation between rs1443434 and NSCL/P.(4)There was no significant correlation between rs10217225 and CPO.The additive model of rs10217225 is related to the occurrence of CL/P(additive model,TT vs CC,OR = 2.236,95% CI = 1.446-3.345,P = 0.000).Conclusions(1)rs3758249 had no significant correlation with CPO.For Chinese,rs3758249 is a risk factor for CL/P and a protective factor for people of other races.(2)rs4460498 is a protective factor for CL/P and CPO.(3)There was no significant correlation between rs1443434 and NSCL/P.(4)There was no significant correlation between rs10217225 and CPO.rs10217225 was a risk factor for CL/P.