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目的探讨线粒体基因及GJB2基因突变与军事噪声性听力损失(noise induced hearing loss,NI HL)易感性的关系,为易感个体的基因筛查及相关分子流行病学研究提供科学依据。方法调查了北京某部349名接触军事噪声的官兵,收集军事噪声性听力损失易感者和耐受者外周血标本182份,提取DNA,PCR扩增线粒体DNA(mitochondrial DNA,mtDNA)目的片段及GJB2编码区,产物直接基因测序。结果基因序列分析共发现98种mtDNA和12种GJB2变异基因型,其中41种存在于12SrRNA;在易感者中发现4例mtDNA突变均为T1095C合并G7642A,在耐受者中未发现该突变;另有3例耐受者均为961delT+insC(其中一人合并235delC杂合),而易感者中未发现该突变。结论证实12SrRNA确为线粒体高突变区。T1095C合并G7642A突变在这些无相同遗传背景但受相同环境因素影响的人群中集中出现,强烈提示该突变可能为导致NI HL的致病性突变。3例有961delT+in-sC的耐受者均长期暴露于噪声环境,这与该突变应为条件致病性突变的推测相符,但与NI HL无明显相关性。
Objective To investigate the relationship between the mutation of mitochondrial gene and GJB2 gene and susceptibility to noise-induced hearing loss (NI HL), and to provide a scientific basis for gene screening and related molecular epidemiological studies of susceptible individuals. Methods A total of 349 military officers and soldiers exposed to military noise in a certain area of Beijing were investigated to collect 182 peripheral blood samples of susceptible and resistant persons with military noise hearing loss. DNA was extracted and the fragment of mitochondrial DNA (mtDNA) was amplified by PCR. GJB2 coding region, the product of direct gene sequencing. RESULTS: A total of 98 mtDNA and 12 GJB2 genotypes were found, of which 41 were found in 12S rRNA. Four of the mtDNA mutations were found to be T1095C and G7642A in susceptible individuals, but not in the tolerant. The other 3 tolerated patients were all 961delT + insC (one of whom had 235delC heterozygous), whereas no mutation was found in susceptible individuals. Conclusion confirmed 12SrRNA indeed mitochondrial hypermutation region. The T1095C merged with the G7642A mutation is concentrated in populations without the same genetic background but affected by the same environmental factors and strongly suggests that the mutation may be the causative mutation that led to NI HL. Long-term exposure of 3 961delT + in-sC tolerant patients to noise was consistent with the speculation that this mutation should be a conditional pathogenic mutation but not with NI HL.