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

Authors
 Hye Jung Park  ;  Young Joo Kim  ;  Dong Hyun Kim  ;  Junho Kim  ;  Kyung Hee Park  ;  Jung-Won Park  ;  Jae-Hyun Lee 
Citation
 Yonsei Medical Journal, Vol.57(1) : 118-126, 2016 
Journal Title
 Yonsei Medical Journal 
ISSN
 0513-5796 
Issue Date
2016
MeSH
Adult ; Aged ; Alleles* ; Allopurinol/adverse effects ; Allopurinol/pharmacology* ; Anticonvulsants/adverse effects* ; Asian Continental Ancestry Group/genetics* ; Carbamazepine/adverse effects ; Carbamazepine/pharmacology* ; Case-Control Studies ; Drug-Related Side Effects and Adverse Reactions/genetics* ; Drug-Related Side Effects and Adverse Reactions/immunology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; HLA-B Antigens/genetics* ; Humans ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stevens-Johnson Syndrome/ethnology ; Stevens-Johnson Syndrome/etiology ; Stevens-Johnson Syndrome/genetics* ; Triazines/adverse effects ; Triazines/pharmacology*
Keywords
Allopurinol ; HLA-B*58:01 ; Stevens-Johnson syndrome ; human leukocyte antigen ; toxic epidermal necrolysis
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*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 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; 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 experienced SJS/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.
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DOI
10.3349/ymj.2016.57.1.118
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김동현(Kim, Dong Hyun)
김영주(Kim, Young Ju)
김준호(Kim, Junho)
박경희(Park, Kyung Hee) ORCID logo https://orcid.org/0000-0003-3605-5364
박중원(Park, Jung Won)
박혜정(Park, Hye Jung) ORCID logo https://orcid.org/0000-0002-1862-1003
이재현(Lee, Jae Hyun) ORCID logo https://orcid.org/0000-0002-0760-0071
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146446
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