title: Association between HLA and Stevens-Johnson syndrome induced by carbamazepine in Southern Han Chinese: genetic markers besides B*1502?
abstract: Previous studies have demonstrated a strong association between carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-induced SJS/TEN) and HLA-B*1502 in Chinese, and HLA-A*3101 but not HLA-B*1502 in Caucasians and Japanese. Cases with CBZ-induced SJS/TEN negative for HLA-B*1502 were reported recently in Southeast Asia. Negative correlations between CBZ-induced SJS/TEN and B*0702 or B*4001 have also been reported, suggesting a possible protective role. Here, we genotyped HLA-B and HLA-A in 18 cases with CBZ-induced SJS/TEN, in comparison with CBZ-tolerant and normal controls in Southern Han Chinese. A strong association between HLA-B*1502 and CBZ-induced SJS/TEN was found, with 72.2% sensitivity and 87.1% specificity. However, we also found five patients with SJS (5/18, 27.78%) who were negative for HLA-B*1502. HLA-A*2402 was present in nine of 16 cases with SJS (56.25%, including three of five cases negative for HLA-B*1502), which was significantly more frequent than that of CBZ-tolerant controls or the general southern population. Only one case with SJS carried HLA-A*3101. No statistical difference in the mean age, sex ratio and CBZ usage was found between the CBZ-induced SJS/TEN group and the CBZ-tolerant group. In search for possible protective genetic markers in HLA-B*1502-positive but CBZ-tolerant patients, we failed to find any significant factors in the HLA alleles observed. Given the association between HLA-B*1502 and CBZ-induced SJS/TEN, genetic testing before initiating CBZ therapy is suggested in Han Chinese population. However, physicians should also be vigilant about SJS/TEN in those negative for HLA-B*1502. Other factors for the development of CBZ-induced SJS/TEN in HLA-B*1502-negative patients and protective factors in CBZ-tolerant patients should be investigated further.
authors.affiliation: Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, Guangzhou, China.
authors.forename: Yi-Wu
authors.initials: YW
authors.lastname: Shi
authors.forename: Fu-Li
authors.initials: FL
authors.lastname: Min
authors.forename: Bin
authors.initials: B
authors.lastname: Qin
authors.forename: Xin
authors.initials: X
authors.lastname: Zou
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Liu
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Gao
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Jue-Qian
authors.initials: JQ
authors.lastname: Zhou
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liao
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000633:toxicity*; D002648:Child; D002681:China; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D059910:HLA-B15 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D015234:HLA-A Antigens; C506273:HLA-A*31:01 antigen; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine