军事噪声性听力损失群体中mtDNA和GJB2基因变异研究

Mitochondrial DNA and GJB2 Genovariation in Noise-Induced Hearing Loss in the Army

张艳;戴朴;薛希均;韩东一;王国建;袁永一;韩冰;陈良飞;钟玲;任黎;孙林辉;陈克久;杨晓东;张培华;张波;杨有声;王顺跃;张金淑;

1:解放军昆明总医院

2:昆明医学院教学医院耳鼻咽喉头颈外科

3:解放军总医院耳鼻咽喉头颈外科

4:解放军77200部队

摘要
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。
关键词
噪声性聋;线粒体DNA;GJB2;基因突变
基金项目(Foundation):
全军医药卫生科研基金课题科技攻关项目(06G110);; 全军医药卫生科研基金课题面上项目资助(06MA142)
作者
张艳;戴朴;薛希均;韩东一;王国建;袁永一;韩冰;陈良飞;钟玲;任黎;孙林辉;陈克久;杨晓东;张培华;张波;杨有声;王顺跃;张金淑;
参考文献

1 Sli winiska-Kowalska M,Pawelczyk M,Kowalski TJ.Geneticfactorsin susceptibility to age-and noise-ralated hearingloss[J].Pol Merkur Lekarski,2006,21:384.

2 Harding GW,Bohne BA,Vos JD,et al.The effect of an age-related hearing loss gene(ahl)on noise-induced hearing lossand cochlear damage fromlow-freqence nosie[J].HearingResearch,2005,204:90.

3 Chen GD.Prestin gene expressionin the rat cochlea followingintense noise exposure[J].Hear Res,2006,222:54.

4吕胜乔,赵一鸣.噪声性耳聋易感基因研究的进展[J].中华预防医学杂志,2003,37:288.

5 Fredelius L.Ti me sequence of degeneration pattern of the organ ofCorti after acoustic over sti mulation:a transmission electron micro-scope study[J].Acta Otolaryngol,1988,106:373.

6韩维举.人听觉器官线粒体DNA4977缺失与老年性聋的关系[J].中华耳鼻咽喉科杂志,2000,35:416.

7韩维举.噪声暴露引起大鼠听觉器官线粒体DNA缺失[J].中华耳鼻咽喉科杂志,2003,38:324.

8顾瑞,陈洪文,姚治中.军事噪声性听力损失诊断标准及处理原则[J].解放军预防医学杂志,1995,13:337.

9 Hyde GE,Rubel EW.Mitochondrial role in hair cell surivivalafter injury[J].Otolaryhyol Head Neck Surg,1995,113:530.

10 Han W,Shi X,Nuttall AL.AIFand endoGtranslocationin noiseexposureinduced hair cell death[J].Hear Res,2006,211:85.

11 Li Z,Li R,Chen J,et al.Mutational analysis of the mito-chondrial 12S rRNA gene in Chinese pediatric subjects withaminoglycoside-induced and non-syndromic hearing loss[J].Hum Genet,2005,117:9.

12 Thyagarajan D,Bressman S,Bruno C,et al.A novel mito-chondrial 12SrRNA point mutation in parkinsonism,deaf-ness,and neuropathy[J].Ann Neurol,2002,48:730.

13 Tessa A,Giannotti A,Tieri L,et al.Matemallyinherited deaf-ness associated with a T1095C mutation in the mtDNA[J].Eur J Hum Genet,2001,9:147.

14 Zhao LD,Young WY,Li RI,et al.Clinical evaluation and se-quence analysis of the complete mitochondrial genome of threeChinese patients with hearingi mpairment associated with the12S rRNA T1095C mutation[J].Biochem Biophys Res Com-mum,2004,325:1 503.

15 Li X,Fischel-Ghodsian N,Schwartz F,et al.Biochemicalcharacterization of the mitochondrial tRNASer(UCN)T7511C mutation associated with nonsyndromic deafness[J].Nucleic Acids Res,2004,32:867.

16 Yoshida M,Shintani T,Hirao M,et al.Aminoglycoside-in-duced hearinglossin a patient withthe 961 mutaitionin mtD-NA[J].ORL J Otorhinolaryngol Relat Spec,2002,64:219.

17曹新,邢光前,魏歆俊,等.线粒体DNA A1555G和961 insC双重突变导致的非综合征型遗传性耳聋[J].中华医学遗传学杂志,2004,6:29.

18 Zelante L,Gasparini P,Estivill X,et al.Connexin26 muta-tions associated with the most common form of non-syn-dromic neurosensory autosomal recessive deafness(DFNB1)in Mediterraneans[J].Hum Mol Genet,1997,6:1 605.

19 Abe S,Usami S,Shinkawa H,et al.Prevalent connexin 26 gene(GJB2)mutationsin Japanese[J].J Med Genet,2000,37:41.

20戴朴,刘新,于飞,等.18个省市聋校学生非综合征型聋病分子流行病学研究(I)[J].中华耳科学杂志,2004,2:37.

21 Van Eyken E,Van Laer L,Fransen E,et al.The Contribution ofGJB2(Connexin 26)35delG to age-related hearing i mpairmentand noise-induced hearingloss[J].Otol Neurotol,2007,28:970.

22 Wattanasirichaigoon D,Li mwongse C,Jariengprasert C,et al.High prevalence of V37I genetic variant in the connexin-26(GJB2)gene among non-syndromic hearing-i mpaired andcontrol Thai individuals[J].Clin Genet,2004,66:452.

23贺定华,冯永,夏昆,等.GJB2基因在遗传性聋中的检测[J].听力学及言语疾病杂志,2005,13:301.

24李庆忠,王秋菊,韩东一,等.GJB2基因突变始祖效应对中国耳聋人群的影响[J].解放军医学杂志,2005,30:394.