The Study Of The Association Between The Susceptibility Sites Of Cleft Lip And Palate And MicroRNA Polymorphisms And The Susceptibility Of Non-syndromic Congenital Tooth Loss

PartⅠ Non-syndromic cleft lip with or without palate susceptible loci are associated with tooth agenesis Objective: Non-syndromic tooth agenesis(NSTA)may share common genetic factors with non-syndromic cleft lip with or without cleft palate(NSCL/P).Single nucleotide polymorphisms(SNPs)were associated with individual?s susceptibility to these anomalies.We selected five NSCL/P-associated SNPs from our previous genome-wide association study(GWAS)to test for the associations with NSTA.Materials and methods: 677 NSTA cases and 1,144 healthy controls were recruited in this case-control study.Five genome-wide NSCL/P-associated SNPs(rs2235371,rs7078160,rs8049367,rs4791774 and rs13041247)were genotyped by Taq Man platform and evaluated for the associations with NSTA using PLINK software.Results: No significant associations between these SNPs and risk of NSTA were observed in the overall analysis and subgroup analysis with the number of missing teeth.However,in the subgroup analysis by tooth position,rs8049367 was nominally associated with mandibular premolar agenesis(Dominant model: ORdom=0.66,95% CIdom=0.47-0.93,Pdom=0.016;Heterozygote model: ORhet=0.60,95% CIhet=0.41-0.88,Phet=0.008).Rs4791774 showed a nominal association with congenitally missing maxillary canine(Dominant model: ORdom=0.53,95% CIdom=0.28-0.98,Pdom=0.041;Heterozygote model: ORhet=0.50,95% CIhet=0.26-0.97,Phet=0.041)and premolar(Additive model: OR=0.59,95% CI=0.36-0.96,P=0.035).Conclusion: This study showed that NSCL/P susceptible loci rs8049367 and rs4791774 were probably associated with risk of NSTA.Part Ⅱ Genetic Variants of mi RNAs and Risk of Non-syndromic Tooth Agenesis Background: Non-syndromic tooth agenesis(NSTA)is one of the most common dental abnormalities.Micro RNAs participated in the craniofacial and tooth development.Therefore,single nucleotide polymorphisms(SNPs)in mi RNA genes may contribute to susceptibility of NSTA.Materials and methods: 677 NSTA cases and 1,144 healthy controls were recruited and four mi RNA SNPs(mi R-146 a rs2910164,mi R-196a2 rs11614913,mi R-605 rs2043556,mi R-618 rs2682818)were genotyped by Taq Man platform.The association between these four SNPs and NSTA susceptibility was evaluated by PLINK software(version 1.07).Results: Rs2043556 showed an association with NSTA risk(Homozygote model: P=0.031,OR=1.49,95% CI=1.04-2.13)in overall analysis.Additionally,in subgroup analysis,rs2043556 was associated with hypodontia(Homozygote model: P=0.034,OR=1.48,95% CI=1.03-2.13),upper lateral incisor agenesis(Homozygote model: P=0.023,OR=2.09,95% CI=1.11-3.94),upper canineagenesis(Additive model: P=0.007,OR=1.69,95% CI=1.16-2.47)and lower incisor agenesis(Additive model: P=0.044,OR=1.21,95% CI=1.01-1.45).Rs2910164 was in association with the agenesis of upper central incisor(Additive model: P=0.014,OR=2.49,95% CI=1.21-5.15),upper molar(Recessive model: P=0.018,OR=4.04,95% CI=1.27-12.89)and lower premolar(Heterozygote model: P=0.039;OR=0.68,95% CI=0.47-0.98).Conclusion: This study indicatedthatgenetic variants of mi RNA were associated with risk of non-syndromic tooth agenesis.