HLA-A31 strongly associates with carbamazepine-induced adverse drug reactions but not with carbamazepine-induced lymphocyte proliferation in a Japanese population.

Abstract

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.

• Authors: Hiroyuki Niihara, Takeyasu Kakamu, Yasuyuki Fujita, Sakae Kaneko, Eishin Morita
• Journal: The Journal of dermatology (J Dermatol) Vol. 39 Issue 7 Pg. 594-601 (Jul 2012) ISSN: 1346-8138 [Electronic] England
• PMID: 22211527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Japanese Dermatological Association.

Chemical References

• Anticonvulsants
• HLA-A Antigens
• HLA-A31 antigen
• Carbamazepine

Topics

• Adult
• Aged
• Amino Acid Sequence
• Anticonvulsants (adverse effects, immunology)
• Asian People (genetics)
• Carbamazepine (adverse effects, immunology)
• Case-Control Studies
• Drug Eruptions (genetics, immunology)
• Female
• Gene Frequency
• Genetic Association Studies
• HLA-A Antigens (genetics)
• Humans
• Japan
• Lymphocyte Activation (drug effects)
• Male
• Middle Aged
• Molecular Sequence Data
• Stevens-Johnson Syndrome (chemically induced, genetics, immunology)
• Young Adult