中国非综合征型聋患者GJB2基因突变流行病学文献荟萃分析

摘要

目的 综合分析GJB2基因在我国非综合征型感音神经性聋人群中的流行病学特征,发现既往研究中可能存在的问题并提出解决方案.方法 通过万方数据库和Pubmed数据库检索2000年1月～2010年8月间国内外期刊刊登的有关GJB2基因突变流行病学文献,制定文献纳入标准和排除标准,采用荟萃分析方法对各文献研究样本状况及GJB2基因突变的流行病学数据进行统计描述,综合分析GJB2基因在我国的总体突变频率及突变热点的总体等位基因频率等数据.结果 纳入文献32篇,研究样本量14～2 063例,致病突变频率0%～28.57%,致病突变携带频率0%～38.33%;GJB2总体致病突变频率为12.88%(1 028/7 984),总体致病突变携带频率为19.41%(1 575/8 115);4种常见突变热点c.235delC、c.299_300delAT、c.176_191del16和c.35delG的总体等位基因频率分别为11.90%、2.22%、0.65%和0.27%.语前聋患者中GJB2基因的致病突变频率高于语后聋患者,人工耳蜗植入患者中GJB2基因的致病突变频率高于总体致病突变频率(P＜0.05).结论 GJB2基因突变是我国非综合征型感音神经性聋人群重要的分子病因之一,GJB2基因最为常见的突变类型是c.235delC,其次是c.299_300delAT,c.176_191del16和c.35delG;其流行病学研究中存在样本量不足和样本纳入标准不规范的问题.%Objective To analyze epidemiological data obtained from present studies with regards to GJB2 mutation in Chinese populations with non-syndromic sensorineural hearing loss by the Meta analysis and to evaluate the reliability of the epidemiological studies. Methods Published epidemiological studies of Chinese GJB2 mutation were collected from January, 2000 to August, 2010 from the WanFang database and PUBMED. The criteria for the literature assessment were established. Meta analysis was carried to study the data such as pathogenic mutation frequency, carrying frequency, mutant allele frequency of hot spots and so on. Results 32 studies were included and the samples arranged from 14 to 2 063. Reported pathogenic mutation frequency and carrying frequency were from 0%~28. 57% and 0%~38. 33%,respectively. The integrating pathogenic mutation frequency and carrying frequency were 12.88% (1 028/7 984) and 19. 41% (1 575/8 115). The integrating mutant allele frequencies of four the most common mutation hot spots of c. 235delC,c. 299_300delAT,c. 176_191dell6 and c. 35delG were 11. 90%, 2. 22% ,0. 65% and 0. 27%. The pathogenic mutation frequency of GJB2 was higher in patients with prelingual deafness than in patients with post lingual deafness, and that for cochlear implant recipients was higher than the integrating pathogenic mutation frequency (P<0. 05). Conclusion GJB2 mutation was one of the most important factors causing deafness in China. The most common mutation was c. 235delC, followed by c 299_300delAT,c. 176_191dell6and c. 35delG. There were some deficiencies in GJB2 epidemiological research such as a lack of samples compounded by non-standard sample inclusion criteria. It was necessary to establish a unified and normalized standard in epidemiological studies in China.