Association between the DRB1*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.


METHODS
Case-control study.


METHODS
Kuma Hospital, which specializes in thyroid diseases, in Kobe, Japan.


METHODS
24 patients with Graves disease who had methimazole-induced agranulocytosis diagnosed by peripheral granulocyte counts of less than 0.5 x 10(9)/L, and 68 patients with Graves disease treated with methimazole, who were free from agranulocytosis. Controls were 525 healthy, unrelated Japanese student volunteers at Kyushu University in Japan.


METHODS
All HLA class II genes were analyzed for polymorphisms at the DNA level by using the polymerase chain reaction sequence-specific oligonucleotide probes method. The allele frequencies in the agranulocytotic Graves disease group were compared with those in the nonagranulocytotic Graves disease and control groups.


RESULTS
A strong positive association was seen in DRB1*08032 between the agranulocytotic group and both the control and nonagranulocytotic Graves disease groups.


CONCLUSIONS
The HLA DRB1*08032 allele was strongly associated with susceptibility to methimazole-induced agranulocytosis, suggesting that cellular autoimmunity may be involved in its development.
Tamai
H
H
Kyushu University, Fukuoka, Japan.
Sudo
T
T
Kimura
A
A
Mukuta
T
T
Matsubayashi
S
S
Kuma
K
K
Nagataki
S
S
Sasazuki
T
T
D000380:Agranulocytosis / Q000139:chemically induced*; D013956:Antithyroid Agents / Q000009:adverse effects*; D015551:Autoimmunity; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008713:Methimazole / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology
D013956:Antithyroid Agents; D006684:HLA-DR Antigens; D008713:Methimazole