Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population.
Antiepileptic drugs including lamotrigine (LTG) and carbamazepine (CBZ) are among the most common causes of cutaneous adverse reactions (cADRs). Human leukocyte antigen (HLA)-B*1502 has been strongly associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To investigate this relationship, we performed high-resolution HLA genotyping on LTG-tolerant controls, healthy volunteers, and patients affected by LTG-induced cADRs, ranging from maculopapular exanthema (MPE) to SJS/TEN. Patients with LTG-induced cADRs (n=25, including three with SJS/TEN and 22 with MPE), 21 LTG-tolerant controls, and 71 healthy volunteers were enrolled. The differences in the starting dosage of LTG among the SJS/TEN, MPE, and LTG-tolerant control groups were not statistically significant. HLA-B*1502 frequency was 33.3% (1/3; LTG-induced SJS/TEN group), 9.1% (2/22; LTG-induced MPE group), 4.8% (1/21; LTG-tolerant group), and 8.5% (6/71; healthy volunteers). There was no significant difference in the frequency of subjects with the HLA-B*1502 allele between the SJS/TEN group and LTG-tolerant group (p=0.239, OR=10.0, 95% CI 0.44-228.7), and healthy volunteers (p=0.26, OR=5.42, 95% CI 0.43-68.8), MPE and LTG-tolerant groups (p=1.0, OR=1.08, 95% CI 0.20-5.8), and healthy volunteers (p=1.0, OR=2.0, 95% CI 0.17-23.9). None of the HLA alleles detected were associated with LTG-induced cADRs. In conclusion, HLA-B*1502 and other HLA alleles are not directly associated with LTG-induced MPE. The possibility that HLA-B*1502 is associated with an increased risk of LTG-induced SJS/TEN could not be excluded.
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China.
Dong-Mei
DM
An
Xin-Tong
XT
Wu
Fa-Yun
FY
Hu
Bo
B
Yan
Hermann
H
Stefan
Dong
D
Zhou
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000208:ethnology; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced*; D014227:Triazines / Q000009:adverse effects*; D014582:Urticaria Pigmentosa / Q000139:chemically induced*; D055815:Young Adult
D000927:Anticonvulsants; D015235:HLA-B Antigens; D014227:Triazines; D000077213:Lamotrigine