Presentation: HLA Allele Frequencies in 5,802 Koreans: Varied Allele Types Associated with SJS/Ten According to Culprit Drugs ( World Allergy Congress)

Thursday, 15 October 2015

Hall D1 Foyer (Floor 3) (Coex Convention Center)

Hye Jung Park, MD , Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Young Joo Kim, MD , Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Dong Hyun Kim, MD , Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Junho Kim, MD , Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Kyung Hee Park, MD , Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Jung-Won Park, MD, PhD , Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Jae-Hyun Lee, MD, PhD , Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Background: 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 certain human leukocyte antigen (HLA) gene type. We aimed to figure out HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea.

Methods: We enrolled 5,802 subjects who had results of HLA typing test from Aug. 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: Among HLA-A genes, the most frequent allele type was HLA-A* 24:02 (20.5%) followed by HLA-A*33:03 (16.8%). HLA-B*44:03 (10.0%) and HLA-Cw*01:02 (17.1%) was the most frequent type in HLA-B, -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 possessed HLA-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; 7.12-463.50; P <0.001). HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (Odds ratio: 12.75, 1.03-157.14, P = 0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03.

Conclusions: HLA Gene frequencies varied in Korea. Screening of HLA-B*58:01 before use of allopurinol might be needed to anticipate probability of SJS/TEN. HLA gene associated lamotrigine or carbamazepine-induced SJS/TEN should be further studied.

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