中国汉族人群结核易感基因多态性与耐药结核病相关性研究  

Study on the correlation between polymorphisms of genes with susceptibility to tuberculosis and drug-resistant tuberculosis in Chinese Han population

作　　者：刘一典[1] 郑瑞娟[1] 肖和平[1] 沙巍[1] 张青[1] 吴福蓉[1] 孙华[1] 张忠顺[1] 崔海燕[1] 刘轾彬[1] 唐神结[1] 

机构地区：[1]同济大学附属上海市肺科医院结核病诊疗中心上海市结核(肺)重点实验室,上海200433

出　　处：《中华流行病学杂志》2011年第3期279-284,共6页Chinese Journal of Epidemiology

基　　金：基金项目：“十一五”国家科技重大专项（2009ZX10003-017）;上海市基础研究重点项目（08JC1420000）

摘　　要：目的 了解结核易感基因SLC11A1基因、VDR基因、MBL基因以及IFNG基因多态性在中国汉族人群敏感和耐药结核病患者中的分布,探讨其与耐药结核病发生的相关性.方法 使用焦磷酸测序法、Real-time探针法、SNaPshot法测定229例敏感肺结核（敏感组）和230例耐药肺结核（耐药组）患者的VDR基因、SLC11A1基因、MBL基因、IFNG基因的单核苷酸多态性（SNP）.结果 VDR基因多态性位点在敏感组和耐药组间差异均无统计学意义（P＞0.05）.SLC11A1基因的INT4位点基因型和等位基因频率在敏感组和耐药组间差异有统计学意义（P值分别为0.031、0.046）;INT4位点在隐性遗传模型假定下,敏感组和耐药组间差异具有统计学意义（OR=5.756,95%CI：1.261～26.269,P=0.011）,结合该位点各种组合下的OR值间的数量关系,确定该位点的遗传模型符合隐性遗传模型.MBL基因Q/P位点基因型和等位基因频率在敏感组和耐药组间差异有统计学意义（P值分别为0.029、0.033）;在隐性遗传模型假定下,MBL基因Q/P位点基因型和等位基因频率在不同组别间差异有统计学意义（OR=9.290,95%CI：1.167～73.949,P=0.011）.IFNG基因的多态性位点在敏感组和耐药组之间的分布无统计学意义.结论 SLC11A1基因的INT4位点和MBL基因Q/P位点可能与中国汉族人群耐药结核病的发生具有一定的相关性.Objective To investigate the distribution of polymorphisms of SLC11A1 gene,VDR gene,MBL gene and IFNG gene with susceptibility to tuberculosis （TB） in Chinese Han population suffering from drug-sensitive TB and drug-resistant TB so as to identify the correlation between gene polymorphisms and the development of drug-resistant TB.Methods Single nucleotide polymorphisms （SNP） of VDR gene,SLC11A1 gene,MBL gene,IFNG gene were typed and analyzed by pyrosequencing,Real-time Probe and SNaPshot among 229 patients with drug-sensitive TB and 230 patients with drug-resistant TB.Results The polymorphic foci of VDR gene from the drug-sensitive TB group and the drug-resistant TB group showed no significant difference （P〉0.05）.The genotype of INT4 site and allelic frequency of SLC11A1 gene for drug-sensitive TB group were significantly different from those for drug-resistant TB group（P=0.031,0.046）.If recessive inheritance was assumed,the genotypes of INT4 site from the two groups were significantly different （0R=5.756,95% CI：1.261-26.269,P=0.011）.Considering the relationship between OR values under various combination,our findings confirmed that the genetic mode of INT4 site was in accordance with recessive inheritance.The genotypes of Q/P site and allelic frequencies of MBL gene from drug-sensitive and drug-resistant groups were significantly different （P=0.029,0.033）.The difference still existed under the hypothesis of recessive inheritance （OR=9.290,95% CI：1.167-73.949,P=0.011）.The polymorphic foci of IFNG gene from the two groups showed no significant difference.Conclusion INT4 sites on SLC11A1 gene and Q/P site on MBL gene were probably associated with the development of drug-resistant TB in Chinese Han population.Further study on this issue would be helpful in locating the population at high risk of drug-resistant TB and exploring the effective intervention to decrease the incidence of this disease.

关 键 词：结核 肺 抗药性 细菌 易感基因 多态性 

分 类 号：R52[医药卫生—内科学]