遵义市汉族居民Eales病人类白细胞抗原基因多态性和结核感染的相关性研究

Human leukocyte antigen alleles polymorphism in Han nationality suffered from Eales disease or tuberculosis in Zunyi city

目的探讨遵义市汉族Eales病与人类白细胞抗原（HLA）-A／B、HLA—DRB／DQB基因多态性和结核感染的相关性。方法采用聚合酶链反应序列特异引物法（PCR—SSP）检测Eales病组、肺结核组、正常对照组HlA-A／B、HLA—DRB／DQB共59个等位基因分布频率，计算各组间优势比（OR）及95％可信区间（cD；对Eales病组与肺结核组的HLA—A＊02基因分布频率做相关分析。Eales病组为临床确诊的Eales病患者47例；肺结核组为痰结核菌培养确诊肺结核并排除眼部疾病的患者36例；正常对照组为与研究组患者年龄、性别、民族等因素无差异的100名健康人。Easle病组中，资料完整的39例Eales病患者根据病史及纯结核菌素试验（PPD）检查结果分为4组，a组为既往或现在患肺结核患者，12例；b组为无结核感染患者，27例；C组为PPD检查阳性者，27例；d组为PPD阴性者，12例。结果Eales病组HlA—A＊02（OR=9．719，OR95％CI为4．377～21．580，P=0．000）、HLA—B＊07（OR=11．605，OR95％CI为2．397～56．191，P=0．001）基因分布频率高于正常对照组，差异有统计学意义，HLA—A＊11基因分布频率低于正常对照组，差异有统计学意义（OR=0．495，OR95％CI为0．245～1．000，P=0．048）。肺结核组HI．A—DRB＊16（OR=5．215，P=0．049）、HI，A—A＊02（OR=18．87，P=0．000）基因分布频率高于正常对照组，差异有统计学意义，HLA—A＊24基因分布频率低于正常对照组，差异有统计学意义（OR=5．690，P=0．015）。a组与b组，C组与d组比较：HLA—A＊02、HLA—A＊11、HLA—B＊07基因分布频率差异无统计学意义。在Eales病组、肺结核组、正常对照组间，HLA—A＊02、HLA-A＊24、HLA—B＊07、HLA—DRB＊16基因总体分布频率比较，差异均有统计学意义，进一步行7。分割法在Eales病组、肺结核组间两两比较，肺结核组HLA—A＊24基因分布频率低于Eales病组，差异有统计学意义（X^2=7．289，P=0．007），而HLA—A＊02基因分布频率无统计学意义（OR=0．515，P=0．202）。Eales病组与肺结核组HI。A—A＊02基因相关性比较，差异无统计学意义（列联系数0．412，P=0．064）。结论Eales病可能存在遗传易感性，HLA—A＊02和HLA—B＊07可能是遵义市汉族Eales病患者的遗传易感基因，而HLA—A＊11可能是保护基因；HLA—DRB＊16和HLA—A＊02可能是遵义市汉族肺结核病的易感基因，而HLA—A＊24可能是保护基因。HLA—A＊02可能是遵义市汉族人群中Eales病和肺结核病共同的易感基因。

Objective To analyze the relationship of human leukocyte antigen alleles （HLA-A/B, HLA-DRB/DQB） polymorphism and Eales disease, tuberculosis infection in a Han population in Zunyi city of China. Methods The subjects were analyzed by case-control study, which consisted of three groups including Eales disease group （47 patients）, pulmonary tuberculosis group （36 patients） and normal control group （100 healthy people）. Thirty-nine patients in Eales disease group who had complete history were divided into 4 subgroups according to the history and tuberculin PPD test. Twelve patients with past or present pulmonary tuberculosis were in group A, 27 patients without pulmonary tuberculosis were in group B, 27 patients with positive PPD test were in group C, and 12 patients with negative PPD test were in group D. Fifty-nine alleles of HLA-A/B and HLA-DRB/DQB were analyzed by polymerase chain reaction with sequence-specific primers （PCR-SSP） in all subjects. Odds ratios between each group （OR） and 95% confidence interval （CI） were calculated; Frequency distribution of HLA-A ＊ 02 gene were analyzed for the group A and the TB group. Results The frequency distribution of HLA-A ＊ 02 （OR=9. 719, OR 95% CI： 4. 377-21. 580, P=0. 000） and HI.A-B ＊ 07 （OR= 11. 605, OR 95% CI： 2. 397-56. 191, P=0. 001） alleles in Eales disease group were obviously higher than that in normal control group, but frequency distribution of HI.A-A＊ 11 （OR=0.495, OR 95% CI： 0.245-1.000, P=0.048） in Eales disease group was obviously lower than that in normal control group. There was no significant difference in frequency distribution of HLA-A ＊ 02, HLA-A ＊ 11 and HLA-B ＊07 alleles between groups A and B, and between groups C and D （P〉0.05）. The distribution frequency of HLA-A ＊02, HLA-A ＊ 24, HLA B ＊07 and HLA-DRB ＊ 16 alleles among Eales disease group, pulmonary tuberculosis group and control group was statistically different （P〈0.05）. The frequency distribution of HLA A ＊ 24 alleles in pulmonary tuberculosis group was lower than that in Eales disease group （2.2 = 7. 289, P= 0. 007）, but the frequency distribution of HLA-A ＊02 alleles had no significant difference （OR=0. 515, P=0. 202） between two groups. Conclusions The alleles of HLA-A ＊02 and HLA-B ＊07 may be genetic predisposing genes of Eales disease, but HLA-A ＊ 11 alleles may be protective gene in population of Han nationality from Zunyi city. The alleles of HLA-DRB ＊16 and HI.A-A ＊ 02 may be genetic predisposing genes of pulmonay tuberculosis. The alleles of HLA-A＊02 may be a common susceptible gene for Eales disease and pulmonary tuberculosis. HLA-A ＊ 11 and HLA-A ＊ 24 alleles were protective genes of Eales disease and pulmonary tuberculosis respectively.