TY - JOUR
T1 - Genotype-phenotype association between HLA and carbamazepine-induced hypersensitivity reactions
T2 - Strength and clinical correlations
AU - Hsiao, Yi Hsin
AU - Hui, Rosaline Chung Yee
AU - Wu, Tony
AU - Chang, Wan Chun
AU - Hsih, Mo Song
AU - Yang, Chih Hsun
AU - Ho, Hsin Chun
AU - Chang, Ya Ging
AU - Chen, Ming Jing
AU - Lin, Jing Yi
AU - Chen, Ding Ping
AU - Chang, Pi Yueh
AU - Wu, Tsu Lan
AU - Hung, Shuen Iu
AU - Chung, Wen Hung
PY - 2014/2
Y1 - 2014/2
N2 - Background: Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective: To carry out a comprehensive analysis on the clinical spectrum and HLA genotype-phenotype correlations in CBZ-induced hypersensitivity reactions. Methods: We analyzed the clinical information of 194 patients with CBZ hypersensitivity (51 MPE, 23 DRESS, 112 SJS/TEN, and 8 cases with other phenotypes), and 152 CBZ-tolerant controls. All are Han Chinese. We examined the HLA-A/HLA-B genotypes, gene dosage, and drug dosage effects. Results: CBZ-SJS/TEN showed the strongest association with the HLA-B*15:02 allele (Pc=5.8×10-43; odds ratio (OR) (95% CI)=97.6(42.0-226.8)), in which HLA-B*15:02 was identified in all patients (25/25) with SJS/TEN with >5% body surface area (BSA) skin detachment, but lost its 100% association (85.1%, 74/87) in SJS with <5% BSA detachment. In contrast, HLA-B*40:01 showed negative association with CBZ-induced SJS/TEN ((Pc=8.3×10-5; OR (95% CI)=0.22(0.1-0.4)). By comparison, CBZ-induced MPE/DRESS had no association with HLA-B*15:02, but linked to HLA-A*31:01 (Pc=2.7×10-3; OR (95% CI)=6.86(2.4-19.9), and HLA-B*51:01 (Pc=0.01; OR (95% CI)=4.56(2.0-10.5)). No gene dosage or CBZ dosage effects was observed. Conclusion: This study reported the different strength of HLA association with CBZ hypersensitivity in Han Chinese. With the increasing application of pharmacogenetic markers, the HLA genotype-phenotype correlations and the results of the test need to be carefully interpreted for CBZ-induced hypersensitivity reactions.
AB - Background: Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective: To carry out a comprehensive analysis on the clinical spectrum and HLA genotype-phenotype correlations in CBZ-induced hypersensitivity reactions. Methods: We analyzed the clinical information of 194 patients with CBZ hypersensitivity (51 MPE, 23 DRESS, 112 SJS/TEN, and 8 cases with other phenotypes), and 152 CBZ-tolerant controls. All are Han Chinese. We examined the HLA-A/HLA-B genotypes, gene dosage, and drug dosage effects. Results: CBZ-SJS/TEN showed the strongest association with the HLA-B*15:02 allele (Pc=5.8×10-43; odds ratio (OR) (95% CI)=97.6(42.0-226.8)), in which HLA-B*15:02 was identified in all patients (25/25) with SJS/TEN with >5% body surface area (BSA) skin detachment, but lost its 100% association (85.1%, 74/87) in SJS with <5% BSA detachment. In contrast, HLA-B*40:01 showed negative association with CBZ-induced SJS/TEN ((Pc=8.3×10-5; OR (95% CI)=0.22(0.1-0.4)). By comparison, CBZ-induced MPE/DRESS had no association with HLA-B*15:02, but linked to HLA-A*31:01 (Pc=2.7×10-3; OR (95% CI)=6.86(2.4-19.9), and HLA-B*51:01 (Pc=0.01; OR (95% CI)=4.56(2.0-10.5)). No gene dosage or CBZ dosage effects was observed. Conclusion: This study reported the different strength of HLA association with CBZ hypersensitivity in Han Chinese. With the increasing application of pharmacogenetic markers, the HLA genotype-phenotype correlations and the results of the test need to be carefully interpreted for CBZ-induced hypersensitivity reactions.
KW - Carbamazepine
KW - Drug rash with eosinophilia and systemic symptoms
KW - Human leukocyte antigens
KW - Maculopapular exanthema
KW - Stevens-Johnson syndrome
UR - https://www.scopus.com/pages/publications/84891663151
U2 - 10.1016/j.jdermsci.2013.10.003
DO - 10.1016/j.jdermsci.2013.10.003
M3 - 文章
C2 - 24268988
AN - SCOPUS:84891663151
SN - 0923-1811
VL - 73
SP - 101
EP - 109
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
IS - 2
ER -