XYLT1基因多态性与汉族职业人群噪声性听力损失易感性之间的关联
Association between XYLT1 SNPs and noise-induced hearing loss in Chinese Han occupational group
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摘要:
目的 探讨XYLT1基因单核苷酸多态性与汉族职业人群噪声性听力损失易感性之间的关系。
方法 采用病例对照研究方法，选择江苏省内1家纺织厂和1家大型电厂接触噪声的工人为研究对象，共1 956人接受健康检查、问卷调查和纯音听力测试。将双耳高频平均听阈≥ 40 dB者定义为病例组（n=660），双耳高频平均听阈< 40 dB者定义为对照组（n=650）。用声级计检测作业现场的噪声强度，用多功能个体噪声剂量计测量个体噪声暴露水平，并计算工人的累积噪声暴露量（CNE）。利用TaqMan分型技术进行XYLT1基因分型。采用独立样本t检验分析年龄、工龄、噪声暴露时间、噪声暴露水平、CNE、高频听阈的均值在两组间的分布差异；双侧χ2检验分析年龄、性别、吸烟、饮酒等分类变量在两组间的分布差异；利用二元logistic回归模型评估XYLT1位点单核苷酸多态性与NIHL易感性之间的关联水平并对CNE进行分层分析。采用双侧χ2检验进行单倍型分析。
结果 两个工厂选择检测点342个，现场噪声强度范围为75.2~100.0 dB（A）；共抽样了223名作业工人，个体噪声暴露水平范围为68.5~108.1 dB（A）。病例组的噪声暴露时间（227.6±94.8）月大于对照组（218.1±88.4）月，平均高频听阈值（37.2±11.8）dB约是对照组（14.0±4.0）dB的3倍；而病例组的耳部疾病患病率和家族史的比例小于对照组（均P < 0.05）。经年龄、性别、吸烟和饮酒校正后，rs7185607 A等位基因（OR=1.57，95% CI：1.07~2.31）、rs7205152C等位基因（OR=1.63，95% CI：1.12~2.37）、rs7191414 A等位基因（OR=1.70，95% CI：1.01~2.77）、rs12598082 G等位基因（OR=1.76，95% CI：1.27~2.44）和rs2311140 G等位基因（OR=1.85，95% CI：1.34~2.55）会增加NIHL的患病风险，而rs59385104 C等位基因（OR=0.51，95% CI：0.27~0.96）则会降低NIHL的患病风险（均P < 0.05）。当CNE > 100（dB·年）时，与rs7185607位点CC基因型相比，携带CA/AA基因型的个体患NIHL的风险增加（OR=1.60，95% CI：1.16~2.20）；与rs7191414位点TT基因型相比，携带AT/AA基因型的个体患NIHL的风险增加（OR=2.21，95% CI：1.47~3.32）；与rs2311140位点AA基因型相比，携带GA/GG基因型的个体患NIHL的风险增加（OR=1.93，95% CI：1.39~2.71）（均P < 0.05）。当CNE ≤ 100（dB·年）时，与AA基因型相比，rs2311140的GA/GG基因型会增加NIHL的患病风险（OR=2.42，95% CI：1.72~3.41，P < 0.001）。显性模型和隐性模型的结果显示，只有rs2311140 G等位基因在两种模型下会增加NIHL的患病风险（OR=2.22，95% CI：1.39~3.53；OR=2.08，95% CI：1.17~3.68）（均P < 0.05）。单倍型分析结果显示，XYLT1单倍型ATTA（OR=0.580，95% CI：0.422~0.798）和CCTA单倍型（OR=0.496，95% CI：0.355~0.693）是NIHL的保护因素（均P < 0.05）；而单倍型CTTG是NIHL患病的危险因素（OR=1.724，95% CI：1.450~2.049）（P < 0.001）。
结论 XYLT1基因可能是NIHL的易感基因。XYLT1的rs2311140 G等位基因和单倍型CTTG可能是NIHL的潜在易感分子标志物。rs7185607、rs7191414和rs2311140位点多态性与噪声之间的交互作用可能对NIHL具有重要影响。
Abstract:Objective To investigate whether XYLT1 single nucleotide polymorphisms (SNPs) are associated with susceptibility to noiseinduced hearing loss (NIHL) in a Chinese Han occupational group.
Methods A case-control study was performed among workers with exposure to noise in a textile mill and a large-scale power plant in Jiangsu province. A total of 1 956 workers received physical examination, questionnaire survey, and pure-tone audiometry. Those with an average hearing threshold ≥ 40 dB in high frequency were defined as NIHL cases (n=660), and the others as the controls (n=650). The noise intensity of the operation site and individual noise exposure level were measured with sound level meter and multifunctional noise dosimeter, respectively. The cumulative noise exposure (CNE) level was calulated. The genotypes of XYLT1 were determined by TaqMan assay. The distributions of mean values of age, working age, noise exposure level, CNE, and high frequency threshold between the two groups were analyzed by independent-sample t test; the distributions of age, gender, smoking, drinking, and other categorical variables between the two groups were analyzed by two-sided χ2 test; the association between XYLT1 SNPs and susceptibility to NIHL was assessed in a binary logistic regression model, and further stratified by CNE. Two-sided χ2 test was also performed for haplotype analysis.
Results The overall noise exposure level detected in the 342 sites were 75.2-100.0 dB(A), and that in 223 workers were 68.5-108.1 dB(A). The NIHL case group showed longer average noise exposure time(227.6±94.8) months and a three-fold higher average high frequency hearing threshold(37.2±11.8) dB than the control group(218.1±88.4) months, (14.0±4.0) dB, as well as lower prevalence rates of ear disease among participants and their relatives (Ps < 0.05). After adjusting for age, sex, smoking, and drinking, rs7185607 A allele (OR=1.57, 95%CI:1.07-2.31), rs7205152 C allele (OR=1.63, 95%CI:1.12-2.37), rs7191414 A allele (OR=1.70, 95%CI:1.01-2.77), rs12598082 G allele (OR=1.76, 95%CI:1.27-2.44), and rs2311140 G allele (OR=1.85, 95%CI:1.34-2.55) increased the risk of presenting NIHL, while rs59385104 C allele (OR=0.51, 95%CI:0.27-0.96) decreased the risk (Ps < 0.05). When CNE > 100(dB·year), compared with rs7185607 CC genotype, the individuals carrying CA/AA genotype had an increased risk of presenting NIHL(OR=1.60, 95%CI:1.16-2.20); compared with rs7191414 TT genotype, those carrying AT/AA genotype had an increased risk of presenting NIHL(OR=2.21, 95% CI:1.47-3.32); compared with rs2311140 AA genotypes, those carrying GA/GG genotype had an increased risk of presenting NIHL(OR=1.93, 95%CI:1.39-2.71)(Ps < 0.05). When CNE ≤ 100(dB·year), compared with rs2311140AA genotype, carrying GA/GG genotype increased the risk of presenting NIHL(OR=2.42, 95%CI:1.72-3.41, P < 0.001). The results of dominant and recessive models showed that only rs2311140 G allele increased the risk of presenting NIHL in both models (OR=2.22, 95%CI:1.39-3.53; OR=2.08, 95%CI:1.17-3.68)(Ps < 0.05). According to the results of haplotype analysis, XYLT1 haplotype ATTA (OR=0.580, 95%CI:0.422-0.798) and haplotype CCTA (OR=0.496, 95%CI:0.355-0.693) were the protective factors of presenting NIHL (Ps < 0.05); haplotype CTTG was a risk factor of presenting NIHL (OR=1.724, 95%CI:1.450-2.049, P < 0.001).
Conclusion XYLT1 may be a susceptible gene of NIHL. The rs2311140 G allele and haplotype rs7185607 C-rs7205152 T-rs7191414 T-rs12598082G of XYLT1 may be potential susceptible molecular markers of NIHL. The interaction between polymorphism and noise at rs7185607, rs7191414, and rs2311140 may have an important impact on NIHL.
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