HLA-A31 strongly associates with carbamazepine-induced adverse drug reactions but not with carbamazepine-induced lymphocyte proliferation in a Japanese population.
Carbamazepine (CBZ) is the most frequent culprit drug for severe cutaneous adverse drug reactions (ADR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS). A strong association between human leukocyte antigen (HLA)-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese, Thai, Malaysian and Indian populations, but not in Caucasian or Japanese populations. Recent studies showed an association between HLA-A*3101 and CBZ-induced ADR in Caucasian and Japanese populations. We conducted a case-control study to determine HLA genotyping of patients with CBZ-induced ADR in a Japanese population. Fifteen patients with CBZ-induced ADR and 33 subjects who had taken CBZ for more than 3 months without evidence of any ADR as a control were enrolled. In addition, the results of a CBZ-induced lymphocyte stimulation test were compared between the groups. A strong association was found between HLA-A31 and CBZ-induced ADR (P < 0.001), and a weak association was found between HLA-A11 and HLA-B51 with CBZ-induced ADR. No HLA-B*1502 was found in either patients or control subjects. The mean CBZ-induced lymphocyte stimulation index was significantly high in patients with CBZ-induced ADR compared with CBZ-tolerant patients (P < 0.001); however, no significant difference was seen between HLA-A31-positive subjects and HLA-A31-negative subjects in either group. These findings suggest that HLA-A31 is strongly associated with CBZ-induced ADR in the Japanese, but does not determine CBZ-induced lymphocyte proliferation.
Department of Dermatology, Shimane University, Izumo, Shimane, Japan. ofcourse@med.shimane-u.ac.jp
Hiroyuki
H
Niihara
Takeyasu
T
Kakamu
Yasuyuki
Y
Fujita
Sakae
S
Kaneko
Eishin
E
Morita
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000927:Anticonvulsants / Q000009:adverse effects / Q000276:immunology; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000009:adverse effects* / Q000276:immunology; D016022:Case-Control Studies; D003875:Drug Eruptions / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D007564:Japan; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D000927:Anticonvulsants; D015234:HLA-A Antigens; C069527:HLA-A31 antigen; D002220:Carbamazepine