Association Studies On Susceptibility Loci (Gene) Of Two Types Of Non-syndromic Hearing Impairment

Hearing impairment is the most inherited common and highly heterogeneous sensory disorder in humans,which affects 1 in every 1000 children,Genetic causes account up to 50%hearing impairment,of which over 70%are non-syndromic hearing impairment,about 80%non-syndromic hearing impairment is inherited in an autosomal recessive pattern.DFNB1 locus containing GJB2 and GJB6 genes has been reported as a major cause of autosomal recessive non-syndromic hearing loss(ARNSHL)worldwide,which locates at chromosome 13q11-q12 spanning about 43.5kb.So far,over 100 genes have been found out which are responsible for hearing impairment.In China,up to 50%nonsyndromic hearing impairment can be attributed to mutations in the DFNB1 and SLC26A4.The research before only find the mutations of the DFNB1 and SLC26A4,not systematically,so we selected five SNPs in the DFNB1 region,four SNPs in the SLC26A4 gene,using a case-control study between sporadic hearing impairment cases and normal hearing people,who were Chinese Han population coming from Jiangsu province.The nine SNPs were genotyped by ARMS-PCR or sequencing.Allele frequencies,genotype frequencies,haplotypes were calculated on SHEsis software.The single-locus association analysis showed statistically differences of allele and genotype frequencies between cases and controls at rs9315400, rs2274084,235delC and rs982663,indicating that DFNB1 and SLC26A4 are closely associated with sporadic hearing impairment.When we compared the distributions of common haplotypes between cases and controls,we also found significant differences between cases and controls in the haplotype with combined rs2274084 and rs2274083,rs2395911,rs2712218 and rs982663.The haplotypes of rs2274084 and rs2274083 showed that the frequency of C-C was much higher in cases than in controls(P=0.015,OR=3.065,95%CI= 1.192～7.883),suggesting that C-C was a risk haplotype for the sporadic hearing impairment.Conversely,the frequency of haplotype T-T was much lower in cases than in controls(P=0.005,OR=0.541,95%CI=0.349～0.837),and this haplotype might be protective against hearing impairment.The haplotypes of rs2395911,rs2712218 and rs982663 showed that the frequency of G-A-C was much higher in cases than in controls(P=0.002468,OR=1.991,95%CI= 1.267～3.129),suggesting that G-A-C was a risk haplotype for the sporadic hearing impairment.The frequency of haplotype G-G-C was much lower in cases than in controls(P=0.000983,OR=0.211,95%CI=0.076～0.581),and this haplotype might be protective against hearing impairment.