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

Jae-Hyun Lee; 박혜정; 김영주; 김동현; 김준호; 박경희; Park Jung Won

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

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Type: Academic journal

Author: Jae-Hyun Lee 박혜정 김영주 김동현 김준호 박경희 Park Jung Won

Journal: Yonsei University College of Medicine Yonsei Medical Journal Yonsei Medical Journal 제57권 제1호 KCI Accredited Journals

Published: 2016.1

Pages: 118 - 126 (9page)

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

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Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneousadverse 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*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. Results: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 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 possessedHLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 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*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 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 experiencedSJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. Conclusion: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.

#Allopurinol #human leukocyte antigen #HLA-B*58:01 #Stevens-Johnson syndrome #toxic epidermal necrolysis

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Balnyte R

Bastuji-Garin S / 1993 / Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme / Arch Dermatol 129 : 92 ~ 96

Cao ZH / 2012 / HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese / Pharmacogeno

Chiu ML / 2012 / Association between HLA-B*58:01 allele and severe cutaneous adverse reactions with allopurinol in Han Chinese in Hong Kong / Br J Dermatol 167 : 44 ~ 49

Ganesan S / 2011 / Question 2 Should phenytoin and carbamazepine be avoided in Asian populations with the HLA-B*1502positive genetic variant? / Arch Dis Child 96 : 104 ~ 106

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