Abstract
刘一典,郑瑞娟,肖和平,沙巍,张青,吴福蓉,孙华,张忠顺,崔海燕,刘轾彬,唐神结.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[J].Chinese journal of Epidemiology,2011,32(3):279-284
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 Ran population
Received:October 19, 2010  
DOI:
KeyWord: 结核,肺  抗药性,细菌  易感基因  多态性
English Key Word: Pulmonary tuberculosis  Bacterial drug resistance  Susceptibility gene  Polymorphism
FundProject:“十一五”国家科技重大专项(2009ZXl0003-017);上海市基础研究重点项目(08JCl420000)
Author NameAffiliationE-mail
LIU Yidian Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
ZHENG Ruijuan Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
XIAO Heping Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
SHA Wei Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
ZHANG Qing Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
WU Furong Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
SUN Hua Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
ZHANG Zhongshun Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
CUI Haiyan Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
LIU Zhibin Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China  
TANG Shenjie Tuberculosis Diagnosis and Treatment&nter, Shanghai Pulmonary Hospital Affiliated to Tongii University, Tuberculosis Key Laboratory of Shanghai, Shanghai 200433, China tangsjll06@sina.Com 
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Abstract:
      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.
English Abstract:
      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.
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