我国汉族Vogt-Koyanagi-Harada综合征患者人类白细胞抗原DQB1等位基因多态性研究  

Polymorphism of HLA-DQB1 alleles in Chinese Han patients with Vogt-Koyanagi-Harada syndrome

作　　者：闵寒毅[1] 刘英[2] 牛妮芳[2] 张美芬[1] 朱席琳[2] 赵家良[1] 

机构地区：[1]中国医学科学院、中国协和医科大学、北京协和医院眼科眼科研究中心,100730 [2]中国医学科学院、中国协和医科大学国家分子生物学重点实验室基础医学研究所

出　　处：《中华眼科杂志》2007年第4期355-360,共6页Chinese Journal of Ophthalmology

摘　　要：目的探讨人类白细胞抗原（HLA）-DQB1等位基因多态性与沃格特-小柳-原田综合征（VKH）遗传易感相关性及与临床表现的关系。方法应用聚合酶链式反应-序列特异性引物（PCR—SSP），对我国汉族VKH患者和非VKH正常对照者HLA-DQB1等位基因进行分型，分析HLA-DQB1等位基因与患者临床表现的关系。结果收集我国汉族VKH患者88例，非VKH正常对照者88例。VKH患者中男性41例（46．6％），女性47例（53．4％）；发病年龄15—67岁，平均36岁。VKH患者HLA—DQB1各等位基因频率：HLA-DQB1＊0401为31．8％，DQB1＊0201为17．6％，DQB1＊0301／＊0304为17．1％，DQB1＊0602为12．5％，DQB1＊0303为6．8％，DQB1＊0302为6．3％，DQB1＊0402为1．7％，DQB1＊0502为1.7％，DQB1＊0601为1．7％，DQB1＊0501为1．1％，DQB1＊050为31．1％，DQB1＊0604为0．6％；DQB1＊0603未检出。VKH患者中HLA—DQB1＊0401（VKH组31．8％与对照组4．5％比较，r=44．00，P=0．000，OR=9．8，95％口为4．51—21．31）和HLA—DQB1＊0303（VKH组6．82％与对照组0．57％比较，〈=9．67，P=0．002，伽=12．81，95％CI为1.65—99．58）等位基因频率高于正常人对照组，差异有统计学意义。而VKH患者HLA—DQB1＊0601（VKH组1.7％与对照组9．7％比较，r=10．39，P=0．001，OR=0．16，95％CI为0．05—0．56）和HLA—DQB1＊0302（VKH组6．3％与对照组19．3％比较，r=13．48，P=0．000，OR=0．28，95％CI为0．14—0．57）等位基因频率显著低于正常人对照组，差异有统计学意义。HLA-DQB1＊0401阴性患者与阳性患者之间的临床表现差异无统计学意义（P〈0．01）。结论（I）HLA—DQB1＊0401和DQB1＊0303是VKH的易感等位基因，而HLA-DQB1＊0601和DQB1＊0302是抗性等位基因。HLA-DQB1＊0401基因与临床表现无明显相关性。（2）PCR-SSP可用于快速检测HLA—DQB1等位基因型别。Objective To investigate the frequency of HLA-DQBI alleles in Chinese Han patients with Vogt-Koyanngi-Harada syndrome （VKH） and to analyze the relationships among the alleles and clinical manifestations. Methods Eighty-eight Chinese Han patients with VKH and 88 non-VKH normal controls were admitted. DNA was extracted from white blood cells of the subjects by phenol-chloroform method. Thirteen alleles were typed by polymerase chain reaction-sequence specific primer （PCR-SSP）. Relationships among alleles and clinical features were analyzed. Results Twelve of thirteen already known HLA-DQBI alleles were typed by PCR-SSP in patients with VKH. The most frequent allele in patients with VKH was HLA-DQBI ＊ 0401 （ 31.8% ） and this was significantly higher than that of normal controls （31.8% vs. 4.6%, X^2 =44.00,P=0. 000,OR=9.8,95%CI4.51-21.31）. Sowas for HLA-DQBI ＊0303 （6.8% vs. 0.6%, X^2 =9.67,P = 0.002,OR = 12.81,95% CI 1.65-99.58）. On the contrary, the frequency of HLA-DQBI ＊0601 （1.7% vs. 9.7%, X2 =10. 39 ,P =0. 001,0R=0. 16,95%CI0.05-0.56） andHLA-DQBI＇0302 （6.3% vs. 19.3%, X2 =13.48,P=0. 000,OR=0.28,95%CI0. 14-0.57） in patients with VKH were significantly lower than that of normal controls. They found no statistical differences of clinical manifestations such as age of onset, visual acuity, cataract, complicated glaucoma, exudative retinal detachment between HLA-DQB1 ＊ 0401 positive group and HLA-DQB1 ＊ 0401 negative group in patients with VKH. Conclusions （ 1 ） Alleles of HLA-DQB1 ＊ 0401 and HLA-DQB1 ＊ 0303 are susceptible to VKH. HLA-DQB1＊ 0601 and HLA-DQB1＊ 0302 are resistant to VKH. This is the first report that associates HLA-DQB1 ＊ 0302 with resistant of VKH. （2） PCR-SSP is a rapid method for typing the HLA- DQB1 alleles and can be used routinely.

关 键 词：葡萄膜脑膜脑炎综合征 HLA—DQ抗原 等位基因 多态现象(遗传学) 

分 类 号：R686[医药卫生—骨科学]