燃煤型砷中毒患者p16基因缺失及启动区CpG岛甲基化的观察  

Study on p16 gene deletion and promoter 5' CpG island hypomethylation in coal-burning arsenism patients

作　　者：宾海华[1] 张爱华[1] 黄晓欣[2] 潘雪莉[1] 洪峰[1] 蒋宪瑶[1] 

机构地区：[1]贵阳医学院公共卫生学院,550004 [2]中国人民解放军第44医院

出　　处：《中国地方病学杂志》2006年第4期370-373,共4页Chinese Jouranl of Endemiology

基　　金：国家自然科学基金资助项目(30460123);贵州省优秀科技人才及省长专项基金资助项目(黔科教办[2004]07号);贵州省自然科学基金资助项目(黔科合计[2004]3003号)

摘　　要：目的检测燃煤型砷中毒(地砷病)患者p16基因缺失及启动区甲基化的变异,探讨p16基因异常改变在地砷病发生发展乃至癌变过程中的作用。方法采用多重PCR法对103例砷中毒患者和110例正常对照人群p16基因第1、第2外显子缺失情况进行检测;同时采用甲基化特异性PCR法(MSP)和PCR产物测序技术对95例砷中毒患者和100例正常对照人群p16基因启动区甲基化情况进行分析。结果(1)正常对照组p16基因缺失率为5．45％;病例组为14．56％,以第2外显子缺失为主,其中轻、中、重度中毒组p16基因缺失率分别为9．09％、12．50％和19．51％;非癌变组和癌变组p16基因缺失率分别为8．70％和38．89％。以上差异有统计学意义(P<0．05或P<0．01)。(2)对照组p16基因甲基化阳性率为2．00％;病例组为42．11％,其中轻、中、重度中毒组p16基因甲基化阳性率分别为26．32％、41．67％和50．00％;非癌变组和癌变组阳性率分别为21．74％和55．56％。以上差异均有统计学意义(P<0．05或P<0．01)。结论p16基因缺失及启动区甲基化在地砷病的发生发展乃至癌变过程中起重要作用。Objective To detect the situation of p16 gene deletion and hypermethylation of promoter 5＇ CpG island in coal-burning arsenism patients and to analyze the role of the aberrant change of p16 gene in the genesis and development, even carcinogenesis in endemic arsenism. Methods Multi-PCR and methylation-specific polymerase chain reaction （MSP） were respectively performed to analyze p16 exonl and exon2 deletion and hypermethylation of promoter CpG island in arsenism patient group and control group. Simultaneously, PCR products were sequenced to analyze some positive and negative products of MSP. Results （ 1 ）The rate of p16 gene deletion was 5.45% and 14.56% in control group and patients group respectively. The deletion occurred mainly in exon 2. And the deletion rate was respectively 9.09%, 12.50% and 19.51% in mild, moderate and severe arsenism groups. Meanwhile, the deletion rate was 8.70% and 38.89% in non-carcinoma group and carcinoma group, respectively. The variance had statistical significance （P 〈 0.05 or P 〈 0.01 ）. （2）The positive rate of p16 gene promoter CpG island hyermethylation was 42.1% and 2.0% in case group and control group, respectively; it was 26.32%, 41.67% and 50.00% in mild, moderate and severe arsenism groups, and 21.74% and 55.56% in noncarcinoma group and carcinoma group, respectively. The differences were statistically significant （P 〈 0.05 or P 〈 0.01）. Conclusions Deletion and hypomethylation of p16 gene may play an important role in the genesis and development, even carcinogenesis of endemic arsenism.

关 键 词：煤 砷中毒 基因 p16 基因缺失 DNA甲基化 

分 类 号：R599[医药卫生—内科学]