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LMP2/LMP7 基因突变:中国人肠道结核分枝杆菌感染的危险因素。

LMP2/LMP7 gene variant: a risk factor for intestinal Mycobacterium tuberculosis infection in the Chinese population.

机构信息

Department of Anti-Infection and Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.

出版信息

J Gastroenterol Hepatol. 2011 Jul;26(7):1145-50. doi: 10.1111/j.1440-1746.2011.06693.x.

Abstract

BACKGROUND AND AIMS

Low molecular mass protein-2 (LMP2) and low molecular mass protein-7 (LMP7) genes play a critical role in foreign antigen processing on the major histocompatibility complex-I CD8(+) cytotoxic T-lymphocyte pathway. This study was designed to investigate whether the sequence variants in the LMP2/LMP7 coding region were associated with intestinal Mycobacterium tuberculosis (M. tuberculosis) infection or with the co-infection of pulmonary tuberculosis.

METHODS

A total of 168 patients with intestinal tuberculosis and 235 normal controls were recruited for this study. Two polymorphisms of LMP2 (Arg60-His) and LMP7 (Gln145-Lys) were identified by polymerase chain reaction-restriction fragment length polymorphism method. The associations of the LMP2/LMP7 genotype and haplotype with intestinal M. tuberculosis infection were assessed by using logistic regression analysis.

RESULTS

The results revealed that LMP7 position codon 145 Lys/Lys and Gln/Lys alleles in the coding region were associated with the infection of intestinal M. tuberculosis (P=0.003, odds ratio [OR]= 3.86 and P < 0.001, OR = 2.28, respectively). Meanwhile, the Arg-Lys and Cys-Lys haplotypes exhibited significant relation to the intestinal M. tuberculosis infection (P= 0.006, OR=1.87; P=0.021, OR=1.83, respectively). No significant associations were observed for any of the single-nucleotide polymorphism genotypes or haplotypes with the co-infection of pulmonary tuberculosis (P > 0.05).

CONCLUSIONS

The results indicated that the genetic variant within the LMP2/LMP7 gene would increase the risk of intestinal M. tuberculosis infection.

摘要

背景与目的

低相对分子质量蛋白-2(LMP2)和低相对分子质量蛋白-7(LMP7)基因在主要组织相容性复合体-I CD8+细胞毒性 T 淋巴细胞途径上对外来抗原的处理中发挥关键作用。本研究旨在探讨 LMP2/LMP7 编码区序列变异是否与肠道结核分枝杆菌(M. tuberculosis)感染或肺结核的合并感染有关。

方法

共招募了 168 例肠结核患者和 235 例正常对照者进行本研究。采用聚合酶链反应-限制性片段长度多态性方法检测 LMP2(Arg60-His)和 LMP7(Gln145-Lys)的两个多态性。采用 logistic 回归分析评估 LMP2/LMP7 基因型和单倍型与肠道 M. tuberculosis 感染的关系。

结果

结果显示,编码区 LMP7 第 145 位密码子 Lys/Lys 和 Gln/Lys 等位基因与肠道 M. tuberculosis 感染相关(P=0.003,比值比[OR]=3.86 和 P < 0.001,OR=2.28)。同时,Arg-Lys 和 Cys-Lys 单倍型与肠道 M. tuberculosis 感染有显著关系(P=0.006,OR=1.87;P=0.021,OR=1.83)。任何单核苷酸多态性基因型或单倍型与肺结核的合并感染均无显著相关性(P>0.05)。

结论

结果表明,LMP2/LMP7 基因内的遗传变异会增加肠道 M. tuberculosis 感染的风险。

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