| 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].中华流行病学杂志,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 |
| 收稿日期:2010-10-19 出版日期:2014-09-11 |
| DOI： |
| 中文关键词: 结核，肺 抗药性，细菌 易感基因 多态性 |
| 英文关键词: Pulmonary tuberculosis Bacterial drug resistance Susceptibility gene Polymorphism |
| 基金项目:“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) |
| 作者 | 单位 | E-mail | | 刘一典 | 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重点实验室, 上海 200433 | | | 郑瑞娟 | 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重点实验室, 上海 200433 | | | 肖和平 | 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重点实验室, 上海 200433 | | | 沙巍 | 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重点实验室, 上海 200433 | | | 张青 | 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重点实验室, 上海 200433 | | | 吴福蓉 | 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重点实验室, 上海 200433 | | | 孙华 | 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重点实验室, 上海 200433 | | | 张忠顺 | 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重点实验室, 上海 200433 | | | 崔海燕 | 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重点实验室, 上海 200433 | | | 刘轾彬 | 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重点实验室, 上海 200433 | | | 唐神结 | 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重点实验室, 上海 200433 | tangsjll06@sina．Com |
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| 中文摘要: |
| 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. |
| 英文摘要: |
| 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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