LDLR基因多态性与突发性耳聋易感性的关联性分析

Correlation analysis of LDLR gene polymorphisms and susceptibility of sudden sensorineural hearing loss

摘要:

目的探索LDLR基因多态性（single nucleotide polymorphism，SNP）位点与突聋易感性相关性。方法采集139份突聋散发病例和139例无耳疾（听力正常）个体血样，检测血清甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白B水平，提取血液基因组DNA，采用荧光多重酶连接反应技术（improved multiplex ligation detection reaction，iMLDR）及ABI 3730XL测序仪对LDLR基因3个SNPs进行分型。比较两组基因型频率和等位基因型频率的差异，并通过构建基因模型，检验SNPs与突聋易感性的关联性；并比较不同基因型突聋患者的血脂水平。结果突聋组甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白胆固醇（LDLC）水平较对照组显著增高，差异具有统计学意义（P<0.05）；突聋组LDLR基因rs5929（Exton10）位点的T等位基因频率（P=0.022<0.05，OR=1.529，95％CI=1.063-2.198）、rs2738464（Exton18）位点的G等位基因频率（P=0.016<0.05，OR=1.572，95％CI=1.088-2.272）和rs1433099（Exton18）位点的T等位基因频率（P=0.015<0.05，OR=1.578，95％CI=1.090-2.283）显著高于对照组。LDLR基因rs5929位点rs2738464位点及rs1433099位点与突聋易感性有关联。rs5929、rs2738464和rs1433099位点不同基因型患者的血脂水平无统计学差异（P>0.05）。结论甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平升高可能是突聋发病的危险因素，LDLR基因第10外显子区rs5929位点及第18外显子区rs2738464、rs1433099位点与突聋易感性相关；rs5929位点T等位基因、rs2738464位点G等位基因、rs1433099位点T等位基因可能是突聋发病的易感基因，提示携带这三种等位基因的个体可能是突聋发病的高危人群。未发现LDLR基因rs5929、rs2738464、rs1433099位点的不同基因型与血脂水平相关。

关键词:突聋|血脂|LDLR基因|单核苷酸多态性

Abstract:

Abstract:ObjectiveTo explore the correlations between single nucleotide polymorphisms (SNPs) of LDLR gene and susceptibility of sudden sensorineural hearing loss (SSHL). MethodsPeripheral blood specimens were collected from 139 SSHL patients and 139 healthy individuals with normal hearing. Their serum lipid parameters including triglycerides, total cholesterol, highdensity lipoprotein cholesterol, lowdensity lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B were detected. After extraction of blood genomic DNAs, 3 SNPs genotyping were performed using improved multiplex ligation detection reaction (iMLDR) and an ABI 3730XL sequencer. Allele and genotype frequencies between the patients and the controls were compared using the SPSS18.0 software. The correlation between allele frequency of 3 SNPs and susceptibility to SSHL was inspected by construction of gene models. Serum lipid parameters were compared among patients with different genotypes of SSHL.ResultsThe serum levels of triglycerides, total cholesterol and lowdensity lipoprotein cholesterol of the SSHL group were significantly higher than those of the control group respectively, and the differences were statistically significant (all P<0.05). LDLR gene rs5929 (Exton10) T allele frequency (P=0.022<0.05, OR=1.529, 95%CI=1.063-2.198), rs2738464 (Exton18) G allele frequency (P=0.016<0.05, OR=1.572, 95%CI=1.088-2.272) and rs1433099 (Exton18) T allele frequency (P=0.015<0.05, OR=1.578, 95%CI=1.090-2.283) in SSHL group were significantly higher than those of the control group. The statistical correlations were observed between LDLR gene rs5929 T allele and susceptibility to SSHL under dominant genetic model (P=0.031<0.05), rs2738464 G allele under additive and dominant genetic model (P=0.007<0.05); rs1433099 T allele under dominant genetic model (P=0.023<0.05). No correlations were found among the other SNPs polymorphisms and SSHL (P>0.05). In rs5929、rs2738464 and rs1433099 loci, there were no statistically significant differences among serum lipid levels of SSHL patients with different genotypes.ConclusionTotal cholesterol, triglycerides, lowdensity lipoprotein cholesterol may be risk factors in the pathogenesis of SSHL. rs5929 in LDLR gene Exton 10, rs2738464 and rs1433099 in LDLR gene Exton 18 may be associated with susceptibility to SSHL. rs5929 T allele, rs2738464 G allele and rs1433099 T allele may be the risk factors for SSHL. It is suggested that individuals carrying one of these three alleles may be more susceptible to SSHL. No correlations are found between serum lipid levels and different genotypes in rs5929、rs2738464 and rs1433099 loci for SSHL patients.

Key words:Sudden sensorineural hearing loss|Serum lipid| LDLR gene|Single nucleotide polymorphism