ASSOCIATION BETWEEN THE DRB1-ASTERISK-08032 HISTOCOMPATIBILITY ANTIGEN AND METHIMAZOLE-INDUCED AGRANULOCYTOSIS IN JAPANESE PATIENTS WITH GRAVES-DISEASE

Objective: To determine the association between HLA class II genes and methimazole-induced agranulocytosis in patients with Graves disease. Design: Case-control study. Setting: Kuma Hospital, which specializes in thyroid diseases, in Kobe, Japan.Subjects: 24 patients with Graves disease who had methimazole-induced agranulocytosis diagnosed by perip heral granulocyte counts of less than 0.5 x 10(9)/L, and 68 patients w ith Graves disease treated with methimazole, who were free from agranu locytosis. Controls were 525 healthy, unrelated Japanese student volun teers at Kyushu University in Japan. Measurements: All HLA class II ge nes were analyzed for polymorphisms at the DNA level by using the poly merase chain reaction sequence-specific oligonucleotide probes method. The allele frequencies in the agranulocytotic Graves disease group we re compared with those in the nonagranulocytotic Graves disease and co ntrol groups. Results: A strong positive association was seen in DRB1 08032 between the agranulocytotic group and both the control and nonag ranulocytotic Graves disease groups. Conclusion: The HLA DRB108032 al lele was strongly associated with susceptibility to methimazole-induce d agranulocytosis, suggesting that cellular autoimmunity may be involv ed in its development.