人类白细胞抗原与风湿热和风湿性心瓣膜病易感性研究

为探讨人类白细胞抗原（ＨＬＡ）－ＤＱＡ１基因与风湿热（ＲＦ）和风湿性心脏病（ＲＨＤ）患者发病中宿主的遗传关联，选择无亲缘关系的广东籍汉族健康人１０６例和５４例ＲＦ／ＲＨＤ患者，应用聚合酶链反应－聚丙烯酰胺凝胶电泳（ＰＣＲ－ＰＡＧＥ）法，结合高灵敏的银染色作ＨＬＡ－ＤＱＡ１等位基因分型。发现本方法检测的６种ＤＱＡ１等位基因中，ＲＦ／ＲＨＤ组ＤＱＡ１＊０１０１（３１．４８％，相对危险率ＲＲ＝２．８９，Ｐ＜０．００５，病因系数ＥＦ＝０．２０６）明显增高，而ＤＱＡ１＊０１０２（１．８５％，ＲＲ＝０．１０６，Ｐ＜０．００５，预防分数ＰＦ＝０．１３４）显著下降；ＤＱＡ１的两种基因型（＊０１０１／０３０１和＊０１０１／０４０１）在病人组显著增高，而ＤＱＡ１的＊０１０２／０３０１基因型比健康人组明显下降（Ｐ＜０．００５）。上述结果显示：ＨＬＡ－ＤＱＡ１＊０１０１对ＲＦ／ＲＨＤ有遗传易感作用，而ＤＱＡ１＊０１０２有遗传抵抗作用；ＤＱＡ１基因型检测可能为预测ＲＦ／ＲＨＤ易感者提供理论依据。

HLA DQA1 GENES INVOLVED IN GENETIC SUSCEPTIBILITY TO RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN SOUTHERN HANS

The incidence of rheumatic fever (RF) or rheumatic heart disease (RHD) is high in southern China. We studied the genetic susceptibility of HLA-DQA1 alleles to RF or RHD with emphasis on the mechanisms 106 unrelated healthy individuals and 54 patients with RF or RHD of Chinese Han nationality in Guangdong were included. DNA extraction from various biological material using phenol/chloroform method and HLA-DQA1 genotyping by PCR-PAGE and then with silver dyeing was used to show the electrophoretic patterns. A total 6 alleles of HLA-DQA1 were found. Increased allele frequencies of DQA1*0101 (31.48%, RR = 2.89, P < 0.005, EF = 0.206) and decreased allele frequencies of DQA1*0102 (1.85%, RR = 0.106, P < 0.005, PF = 0.134) were observed. Two increased genotyping of HLA-DQA1 (DQA1*0101/0301, chi 2 = 8.84, P < 0.005 and DQA1*0101/0401, chi 2 = 6.23, P < 0.0025) and decreased genotyping of DQA1*0102/0301 (chi 2 = 11.98, P < 0.005) were also observed. These findings suggested that DQA1*0101 contribute to genetic susceptibility for RF or RHD in Guangdong hans while DQA1*0102 to its genetic resistance. Digesting the genotyping of HLA-DQA1 may provide scientific basis for finding susceptible individuals to RF or RHD. Using PCR-PAGE and silver dyeing technique, a new genotyping method for HLA-DQA1, which is simple sensitive and precise, was established and applied.