Association Of The ADAMTS17,USP7 Gene Polymorphisms And Non-syndromic Cleft Lip With Or Without Cleft Palate Among Ningxia Population

Objective: Non-syndromic cleft lip and/or cleft palate is a series of very common congenital malformations.In this study,ADAMTS17 and USP7 genes were selected as candidate genes on the basis of the preliminary research of the research group to explore the correlation between ADAMTS17 and USP7 single nucleotide polymorphisms and non-syndromic cleft lip with or without palate(NSCL±P)in Ningxia population.Methods: Blood samples of 454 children with NSCL±P were collected from the department of oral and maxillofacial surgery,general hospital of Ningxia medical university.5ml of peripheral blood was collected to extract genomic DNA.During the same period,5ml of cord blood and genomic DNA were extracted from 435 normal newborns in the hospital.Genomic DNA concentration,purity,and fragment length were measured,and then DNA parameters were determined.341 common SNPs with MAF > 0.05 on ADAMTS17 gene and 31 common SNPs with MAF > 0.05 on USP7 gene were selected for genotyping.Haploview software was used for the control group’s Hardy-Weinberg equilibrium test and chi-square test of allele frequency of SNP loci between the case group and the control group.SPSS17.0 software was used for chi-square test of genotype frequency of SNP whose allele frequency was less than 0.05 between the two groups.Then Haploview software was used for linkage and haplotype analysis.Results:(1)The gender composition of the case group and the control group in this study is comparable through chi-square test.(2)After the chi-square test of alleles of SNPs conforms the H-W,the allele frequencies of 11 loci,including rs7171763,rs12439275,rs12102063,rs1975454,rs74947098,rs79564799,rs62036166,rs11635943,rs2587762,rs35988728 and rs8039586,were statistically different between the two groups(P < 0.05).The genotype frequency and allele frequency of rs7171763 and rs79564799 were statistically different between the case group and the control group(P<0.05).Haplotype ATGTCAACGCAC in Block 8,haplotype CAATACTCACC in Block 9,haplotype CT and TT in Block 12,CG in Block 13,haplotype AAC in Block 17,haplotype TCCC and CTCA in Block 20,haplotype CCGGGTCCATGTTAG in Block 35,haplotype CCC in Block 51,and haplotype GTTGC in Block 52 were statistically different between the case group and the control group(P < 0.05).(3)After the chi-square test of alleles of USP7 SNPs conforms the H-W,the allele frequencies of 6 SNPs,including rs12929193,rs1677480,rs187614,rs166232,rs2447933 and rs8059146,were statistically different between the case group and the control group(P < 0.05).The genotype frequency and allele frequency of rs12929193 and rs1677480 were statistically different in the case group and the control group(P < 0.05).Haplotype GCCC in Block 3,and haplotype TTT in Block5 were statistically different between the case group and the control group(P < 0.05)。Conclusion:(1)ADAMTS17 SNP sites rs7171763 and rs79564799 are correlated with NSCL±P in Ningxia population.(2)USP7 SNP sites rs12929193 and rs1677480 are associated with NSCL±P in Ningxia population.