Association of HLA-DRB1 allele polymorphism and ANCA with the susceptibility to antithyroid drug-induced leucocytopenia in patients with Graves' disease / 中华内分泌代谢杂志

ABSTRACT

ObjectiveTo investigate the relationship of HLA-DRB1 allele polymorphism and antineutropil cytoplasmic antibody ( ANCA ) with the susceptibility to antithyroid drug ( ATD ) -induced leucocytopenia in the patients with Graves' disease (GD) in Anhui Han Chinese.MethodsThe HLA-DRB1 * 08032,DRB1 * 1501,and DRB1 * 0901 allele frequencies were determined by the polymerase chain reaction-based sequence-specific primer (PCR-SSP) method in 76 patients with Graves' disease who had ATD-induced leucocytopenia and 98 patients with Graves' disease treated with ATD,who were free from leucocytopenia.The other230 healthy subjects served as controls.Indirect immunofluorescence assay (IIF) was used to detect ANCA positive rate.Result( 1 ) Compared with the controls and the GD patients without leucocytopenia,the allele frequencies ofDRB1 * 08032 and DRB1 * 1501 in patients with ATD-induced leucocytopenia were significantly increased ( OR were 3.06,1.77,4.03,and 2.28,all P＜0.05),while that of HLA-DRB1 * 0901 was decreased ( OR were 0.33 and 0.43,both P＜0.05 ).(2)The ANCA frequencies were significantly increased in the GD patients with methimazole-induced leucocytopenia compared with those without leucocytopenia (x2 =4.878,P＜0.05 ).( 3 ) Compared with the GD patients not carrying DRB1 * 08032,DRB1 * 1501,and DRB1 * 0901 alleles,the ANCA positive rates were significantly increased in the GD patients carrying these alleles(x2 were 5.682,5.429,4.009,and 4.549,all P＜0.05).ConclusionsThe DRB1 * 08032 and HLA-DRB1 * 1501 alleles may be susceptible to ATD-induced leucocytopenia in Anhui Hans,while HLA-DRB1 * 0901 alleles may be protective or resistant gene.Immune response may be involved in the development of leucocytopenia.The occurrence of immune response is based on the genetic susceptibility.