Gene Polymorphism Of WNT3, Environmental Risk Factors And Their Interactions In The Development Of Nonsyndromic Cleft Lip With Or Without Cleft Palate In Ningxia

ObjectiveNonsyndromic cleft lip with or without cleft palate is one of the higher incidence ofdisease. Serious impact on human health and quality of life.Up to now its pathogenesy is notclear. It is thought to be a complication that results from an Interaction between geneticbackground and environmental factors now.In the current case control study,the rs142167andthe rs7216231of polymorphisms in WNT3gene were examined to assess their contribution tononsyndromic cleft lip with or without cleft palate.In addition,possible interactions betweenhost genes and environmental factors were explored. The aim of the study is to explore thecause of nonsyndromic cleft lip with or without cleft palate and provide scientific foundationfor relative intervention policies and measures of nonsyndromic cleft lip with or without cleftpalate.Methods1、A hospital-based case control study including631subjects was conducted among373patients of nonsyndromic cleft lip with or without cleft palate and258controls.The caseswere acquired from Ningxia Medical University General Hospital from October in2011toOctober in2012and the controls were acquired from normal newborn in neonatology of thesehospital.A face to face questionnaaire survey was conducted to collect datas.Theenvironmental risk factors were analyzed by logistic regression models and all datas wereanalyzed by PASW18software package.2、Five milliter peripheral blood samples were collected and the total DNAs were extracted for every subject.The rs142167and rs7216231polymorphism in WNT3gene weredetermined with the technique of polymeras chain reaction-restriction fragment lengthpolymorphism(PCR-RFLP)in373nonsyndromic cleft lip with or without cleft palate and258normal newborn. Control analysis、Transmission disequilibrium test(TDT) and Family-basedtest (FBAT).3、The interaction between genes and environmental risk factors was analyzed by logisticregression model.The odds rato values(OR)was calculated by using regression equation todetermine the addition effects among different factors and measure the interactions.Theindexes for quantitative analysis included relative excess risk of interaction(RERI), attributab-le proportion due to interaction (AP) and synergy index (S).Results1、Case-control study found that no difference in cleft lip group，cleft palate group，cleft lipand palate group，cleft lip with or without cleft palate group and the total case groupcompared with the control group at rs142167and rs7216231.There were no difference in Hanpopulation in cleft lip group，cleft palate group，cleft lip and palate group，cleft lip with orwithout cleft palate group and the total case group compared with the control group atrs142167and rs7216231.There were also no difference in Hui population in cleft lip group，cleft palate group，cleft lip and palate group，cleft lip with or without cleft palate group andthe total case group compared with the control group at rs142167and rs7216231.TDT testshowed that rs142167and rs7216231’s allele had not over-transmitted（P＞0.05）in NSCL/P.FBAT test showed that G-G specific haplotypes showed significant over-andunder-transmission.2、Factors that affect the incidence of nonsyndromic cleft lip with or without cleft palate isFather’s smoking history,Mother of passive smoking history and The mother pregnancy inmedication(OR>1), That is risk factors and Father’s drinking history(OR<1)is protectivefactors. 3、(1) No significant incidence that WNT3gene polymorphism onset NSCLP, Statisticalsignificant difference were observed in interactions between rs142167and rs7216231.Between two points is added to the model interaction(2) Father’s smoking history and Father’s drinking history, Father’s smoking history andMother of passive smoking history, Father’s smoking history and The mother pregnancy inmedication, Mother of passive smoking history and Father’s drinking history, The motherpregnancy in medication and Father’s drinking history, Mother of passive smoking history andthe mother pregnancy in medication that additive model has a positive interaction to NSCLP(3)The interaction analysis that there were a positive additive interaction betweenrs142167and Father’s smoking history, Father’s drinking history, The mother pregnancy inmedication.The interaction ananlysis between rs7216231and Father’s smoking history,Father’s drinking history also indicated that there were a positive additive interaction.Conclusion1、NSCLP is recognized that was csused by the interaction between many minor genes andenvironment risk factors with significant genetic heterogeneity, phenotypic complexity andracial differences. The experimental results in a certain extent reflect the existence of racialdifferences and genetic heterogeneity of non-syndromic cleft lip and palate, butenvironmental factors can not be ruled out.2、Environmental factors is an important factor in cleft lip and palate occur, therefore, a goodlifestyle is an important measure to prevent cleft lip and palate occur in the mother duringpregnancy.3、There are a significant interaction between genes-genes, environment-environment andgene-environment.4、Non-syndromic cleft lip and palate is the results of many minor genes coordinating role andinteraction with the environment, to study the relationship between them to clarify theetiology and pathogenesis of non-syndromic cleft lip and palate is of great significance.