HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs

ABSTRACT

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*5801, HLA-B*4403, HLA-B*1502, and HLA-A*3101. RESULTS: HLA-A*2402 (20.5%), HLA-B*4403 (10.0%), and HLA-Cw*0102 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*5801, HLA-B*4403, HLA-A*3101, and HLA-B*1502 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*5801 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*5801 than in subjects without it [odds ratio 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*5801 genotyping, could be more cost-effective than that not based on screening. HLA-B*4403 may be associated with lamotrigine-induced SJS/TEN (odds ratio 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*1502 nor HLA-A*3103. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*5801 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.