中国汉族人群中结核病易感性及耐多药结核病相关基因多态性的相关性研究

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

作者信息

Liu Yi-dian, Zheng Rui-juan, Xiao He-ping, Sha Wei, Zhang Qing, Wu Fu-rong, Sun Hua, Zhang Zhong-shun, Cui Hai-yan, Liu Zhi-bin, Tang Shen-jie

机构信息

Tuberculosis Diagnosis and Treatment Center, Shanghai Pulmonary Hospital Affiliated to Tongji University, Tuberculosis Key Laboratory of Shanghai, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2011 Mar;32(3):279-84.

PMID:21457666

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 (OR = 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.

摘要

目的

研究SLC11A1基因、维生素D受体（VDR）基因、甘露聚糖结合凝集素（MBL）基因及干扰素-γ（IFNG）基因多态性在中国汉族耐多药肺结核及敏感肺结核患者中的分布情况，以明确基因多态性与耐多药肺结核发生发展的相关性。

方法

采用焦磷酸测序、实时荧光探针及SNaPshot技术对229例敏感肺结核患者和230例耐多药肺结核患者的VDR基因、SLC11A1基因、MBL基因及IFNG基因的单核苷酸多态性（SNP）进行分型和分析。

结果

敏感肺结核组与耐多药肺结核组VDR基因多态性位点差异无统计学意义（P>0.05）。敏感肺结核组SLC11A1基因INT4位点基因型及等位基因频率与耐多药肺结核组比较，差异有统计学意义（P=0.031，0.046）。若假定为隐性遗传，两组INT4位点基因型差异有统计学意义（OR=5.756，95%CI：1.261 - 26.269，P=0.011）。综合各组合下OR值的关系，证实INT4位点遗传模式符合隐性遗传。敏感组与耐多药组MBL基因Q/P位点基因型及等位基因频率差异有统计学意义（P=0.029，0.033）。在隐性遗传假设下差异仍存在（OR=9.290，95%CI：1.167 - 73.949，P=0.011）。两组IFNG基因多态性位点差异无统计学意义。