人类白细胞抗原DRB1*和DQB1*基因多态性与尘肺发病的相关性

目的探讨人类白细胞抗原（HIA）DRB1＊和DQB1＊位点基因多态性与尘肺发病的关系。方法采用1：1配比的病例一对照研究方法。尘肺病例组为113名Ⅰ期尘肺患者，对照组为与尘肺病例组年龄相近、同性别、同民族、同一工作地点、开始接尘时间和累积接尘工龄相差不超过2年的接尘工人。用聚合酶链反应序列特异性引物分析方法检测HIA-DRB1＊和DQB1＊共9个位点的等位基因。用SAS6．12软件进行单因素和多因素分析。结果尘肺病例组的HIA—DRB1＊08等位基因频率高于对照组，差异有统计学意义（P〈0.01），OR值为6．000，95％CI：1．906～18．941：HIA—DRB1＊09、HLA—DQB1＊06等位基因频率低于对照组，差异有统计学意义（P〈0．01），OR值为0．259、0．300，95％CI为：0．115～0．584、0．144～0．627；1：1条件logistic回归分析表明，HIA-DRB1＊08、HIA—DRB1＊09和HIA—DQB1＊06等位基因频率与尘肺有关联，调整OR值分别为：7．804、0．225和0．269，95％CI分别为：2．077—29．307、0．083—0．609和0．117～0．613。生存分析表明，HIA—DRB1＊08等位基因为尘肺潜伏期的危险因素；HIA—DQB1＊06为保护因素。结论HIA—DRB1＊08等位基因可能为尘肺易感的危险因素，HLA—DQB1＊06可能是抗尘肺的保护性的等位基因。

Relationship between pneumoconiosis and the polymorphisms of HLA-DRB1 * , DQB1 * genes

OBJECTIVE: To explore the relationship between the polymorphism of HLA-DRB1*, DQB* genes and the susceptibility of pneumoconiosis. METHODS: 1:1 case-control study was adopted. one hundred and thirteen cases of I grade pneumoconiosis were investigated. The control group were workers exposed to dust, who were the same sex, nationality, work place, time of beginning exposure and the cumulative exposure ages not over 2 years. PCR-SSP was used to detect 9 alleles in HLA-DRB1*, DQB1*. Information on related factors of pneumoconiosis was collected using a questionnaire. Univariate and multivariate logistic regression analysis were carried out with 1:1 case-control methodology. RESULTS: The frequency of HLA-DRB1*08 allele in case group was significantly higher than that of the controls (OR: 6.000; 95% CI: 1.9060 - 18.9414). The frequencies of HLA-DRB1*09, HLA-DQB1*06 in case group were significantly lower than those of the controls (OR: 0.259, 0.300; 95% CI: 0.1436 - 0.6268, 0.1149 - 0.5837 respectively). There were significant relationship between HLA-DRB1*08, HLA-DRB1*09, HLA-DQB1*06 alleles and pneumoconiosis after adjusting age, smoking, beginning age of exposure and cumulative length of exposure with multivariate logistic regression analysis (OR: 7.804, 0.225, and 0.269; 95% CI: 2.077 - 29.307, 0.083 - 0.609 and 0.117 - 0.613 respectively. Survival analysis showed that HLA-DQB1*06 allele was a protective factor and HLA-DRB1*08 allele was a risk factor for affecting pneumoconiosis latent period. CONCLUSION: HLA-DRB1*08 allele may be the susceptible risk gene for pneumoconiosis. HLA-DQB1*06 may be the protective gene against developing pneumoconiosis.