HLA-DRB1、DQB1和DPB1等位基因与印度南部肺结核的关系

Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Pub Date : 1999-09-01 DOI:10.1054/tuld.1999.0213

M. Ravikumar , V. Dheenadhayalan , K. Rajaram , S. Shanmuga Lakshmi , P. Paul Kumaran , C.N. Paramasivan , K. Balakrishnan , R.M. Pitchappan

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引用次数: 158

摘要

背景:结核病在印度南部流行;痰阳性肺结核在印度南部和世界上少数其他人群中易患HLA-DR2。目的:研究印度南部肺结核患者及流行人群HLA-DRB1、DQB1、DQA1和DPB1等位基因多态性。设计:采用聚合酶链反应- ssop法对马杜赖地区126例痰阳性肺结核患者和87例地方性对照者进行MHCⅱ类等位基因多态性研究。采用IHWC引物、探针和非放射性探针法。结果:HLA DRB1*1501和DQB1*0601易患肺结核(DRB1*1501:优势比(OR)=2.68, 95%可信区间(CI)=1.30 ~ 5.89, P值(P)=0.013，病因分数(EF)=0.17;DQB1 * 0601: = 2.32, CI = 1.29 - -4.27, P = 0.008, EF = 0.26)。患者单倍型DRB1* 1501-DQB1 *0601高于对照组(1324 / 10000,X2=27.07) (F=404÷10000, X2= 8.84)。在63个种姓匹配样本中，DPB1*04具有预防作用(OR=0.45, CI=0.21-0.95, P=0.036, PF=0.26); DRB1*1501-DQB1*0601-DPB1*04的表型分布在患者和对照组之间存在差异(P=0.0092)。这些等位基因在T5SU种姓的患者和对照组中占主导地位。结论:HLA-DRB1*1501和DQB1*0601易患痰阳性肺结核，DPB1*04具有预防和上位性。种姓T5SU是研究结核病免疫学的理想模型。

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Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India

Setting: Tuberculosis is endemic in south India: sputum positive pulmonary tuberculosis is predisposed by HLA-DR2 in south India and few other populations of the world.

Objective: To study HLA-DRB1, DQB1, DQA1 and DPB1 allelic polymorphism in pulmonary tuberculosis patients and endemic controls from south India.

Design: One hundred and twenty-six, sputum positive pulmonary tuberculosis patients and 87, endemic controls, from Madurai were studied for MHC class II allelic polymorphism by PCR-SSOP method. XI IHWC primers and probes and non-radioactive probing methods were employed.

Results: HLA DRB1*1501 and DQB1*0601 predisposed for pulmonary tuberculosis (DRB1*1501: odds ratio (OR)=2.68, 95% confidence interval (CI)=1.30–5.89, P value (P)=0.013, aetiological fraction (EF)=0.17; DQB1*0601: OR=2.32, CI=1.29–4.27, P=0.008, EF=0.26). Haplotype DRB1*1501–DQB1*0601 was higher in patients (1324 per 10000, X²=27.07) than controls (F=404÷10000, X²= 8.84). In a subset of 63 caste matched samples, DPB1*04 was preventive (OR=0.45, CI=0.21-0.95, P=0.036, PF=0.26): the distributions of DRB1*1501-DQB1*0601-DPB1*04 phenotypes were different between patients and controls (P=0.0092). These alleles were predominant in patients and controls of T5SU caste.

Conclusion: HLA-DRB1*1501 and DQB1*0601 predisposed to sputum positive pulmonary tuberculosis, and DPB1*04 was preventive and epistatic to this risk. Caste T5SU is an ideal model to study immunology of tuberculosis.

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