抗甲状腺药物引起Graves病病人白细胞减少与HLA-DRB1^＊08032及-DRB1^＊1501等位基因相关性

ASSOCIATION BETWEEN HLA-DRB1 ＊ 08032,-DRB1 ＊ 1501 AND ANTITHYROID-DRUG-INDUCED LEUCOCYTOPENIA IN PATIENTS WITH GRAVES DISEASE

目的探讨Graves病(GD)病人应用抗甲状腺药物(ATD)引起白细胞减少与HLA-DRB1*08032、-DRB1*1501的相关性。方法选择130例GD并白细胞减少病人(GDL组),其中应用ATD引起白细胞减少65例(ATDL组),未应用ATD并发白细胞减少65例(NATDL组);非GD病人白细胞减少65例(NGDL组);正常对照65例(CON组)。采用多聚酶链式反应-序列特异引物(PCR-SSP)方法检测各组HLA-DRB1*08032和-DRB1*1501等位基因频率。结果GDL组HLA-DRB1*08032的等位基因频率明显高于CON组和NGDL组(χ2=12.169,P<0.01),ATDL组明显高于NATDL组(χ2=4.032,P<0.05);GDL组HLA-DRB1*1501的等位基因频率明显高于CON组和NGDL组(χ2=12.342,P<0.01),ATDL组明显高于NATDL组(χ2=4.432,P<0.05)。结论GD病人白细胞减少与HLA-DRB1*08032和HLA-DRB1*1501的等位基因表达存在相关性,ATD导致白细胞减少与HLA-DRB1*08032和HLA-DRB1*1501的等位基因频率增加有关。

Objective To determine the association between HLA class Ⅱ genes and ATD-induced leucocytopenia in patients with Graves disease. Methods Recruited into this study were 130 GD patients with leukocytopenia （GDL）, 65 leucocytopeni patients without GD （NGDL） and 65 normol controls （CON）. Of the 130 GD patients, 65 had ATD-induced leukicytopenia （ATDL）, the other 65 were non-ATD-induced leucocytopenia （NATDL）. The frequency of HLA-DRB1 ＊ 08032 and DRB1 ＊ 1501 gene expressions was examined with polymerase chain reaction based sequence-specifec primer （PCR-SSP） method. Results The frequency of HLA-DRB1 ＊ 08032 in GDL group was significantly higher than that in CON and NGDL groups （P〈0.01）. The frequency of HLA-DRB1 ＊ 08032 in ATDL group was significantly higher than that in NATDL group （P〈0.05）. The frequency of HLA-DRB1 ＊ 1501 in GDL group was significantly higher than that in CON and NGDL groups （P〈0.01）. The frequency of HLA- DRB1 ＊ 1501 in ATDL group was significantly higher than that in NATDL group （P〈0.05）. Conclusion GD with leucocytopenia was associated with HLA-DRB1 ＊ 08032 and HLA-DRB1 ＊ 1501 gene expression. ATD-induced leucocytopenia was associated with higher expression of HLA-DRB1 ＊ 08032 and HLA-DRB1 ＊ 1501 gene.