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目的探讨细胞凋亡通路相关基因CASP3和CASP7多态性与中国汉族人群噪声性听力损失(NIHL)易感性之间的关联。方法研究对象来自2014年杭州市1 549名噪声接触工人听力损失的横断面调查,采用1:1配对病例对照研究,病例组为电测听双耳高频平均听阈>25 d B(A)的工人,对照组为性别、年龄、接噪工龄、工作岗位与病例匹配且双耳所有频段听阈均≤25 d B(A)的工人,共272对。PCR-LDR法检测2个SNP位点的基因型。采用多因素条件logistic回归模型分析SNP位点与NIHL的关联,并以叉生分析计算基因-环境交互作用。结果χ~2检验分析发现,CASP3基因rs1049216等位基因(C、T)频率组间分布有统计学差异(OR=0.68,95%CI=0.50~0.93),而基因型频率组间差异无统计学意义(P>0.05);CASP7基因rs10787498等位基因及基因型频率组间分布均无统计学意义(P>0.05);多因素条件logistic回归显示,CASP3基因rs1049216中,与野生基因型CC相比,突变基因型(CT+TT)为NIHL的保护因素(调整OR=0.65,95%CI=0.43~0.97);叉生分析表明rs1049216位点与文化程度、睡眠时间存在交互作用(P≤0.001),NIHL的危险性降低(OR值变小)。结论 CASP3基因rs1049216位点可能与中国汉族人群NIHL易感性有关,且可能与文化程度、睡眠时间存在交互作用。
Objective To investigate the association between CASP3 and CASP7 polymorphisms in apoptosis pathway and susceptibility to noise-induced hearing loss (NIHL) in Chinese Han population. METHODS: The subjects were from a cross-sectional survey of 1 549 noise-exposed workers in Hangzhou City in 2014. A 1: 1 matched case-control study was performed. The patients were examined by audiometry with a hearing threshold of> 25 d B (A) Workers and control groups were 272 pairs of workers with gender, age, length of service received, job matching and cases with hearing thresholds ≤25d B (A) in all binaural bands. The genotypes of two SNPs were detected by PCR-LDR. Multi-factor conditional logistic regression model was used to analyze the association of SNP loci with NIHL, and cross-gene analysis was used to calculate the gene-environment interaction. Results There was a statistically significant difference (rs = 0.68, 95% CI = 0.50 ~ 0.93) in frequencies of rs1049216 allele (C, T) between CASP3 gene and genotypes (P> 0.05). The CASP7 gene rs10787498 allele and genotype frequency distribution between the groups were not statistically significant (P> 0.05); multivariate conditional logistic regression showed that CASP3 gene rs1049216, with the wild genotype CC (OR = 0.65, 95% CI = 0.43-0.97). The cross-breeding analysis showed that there was interaction between rs1049216 locus and education level and sleep time (P≤0.001 ), NIHL reduce the risk (OR value smaller). Conclusion The rs1049216 locus of CASP3 gene may be related to NIHL susceptibility in Chinese Han population, and may have an interaction with educational level and sleep time.