HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol

DOI Web Site 被引用文献82件
  • Shuen-Iu Hung
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Wen-Hung Chung
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Lieh-Bang Liou
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Chen-Chung Chu
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Marie Lin
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Hsien-Ping Huang
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Yen-Ling Lin
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Joung-Liang Lan
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Li-Cheng Yang
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Hong-Shang Hong
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Ming-Jing Chen
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Ping-Chin Lai
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Mai-Szu Wu
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Chia-Yu Chu
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Kuo-Hsien Wang
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Chien-Hsiun Chen
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Cathy S. J. Fann
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Jer-Yuarn Wu
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...
  • Yuan-Tsong Chen
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Departments of Dermatology, Rheumatology, Allergy, and Immunology, and Nephrology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan; Department of Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Dermatology,...

抄録

<jats:p>Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol–SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol–SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol–SCAR and SNPs in the MHC region, including<jats:italic>BAT3</jats:italic>(encoding HLA-B associated transcript 3),<jats:italic>MSH5</jats:italic>(mutS homolog 5), and<jats:italic>MICB</jats:italic>(MHC class I polypeptide-related sequence B) (<jats:italic>P</jats:italic>< 10<jats:sup>–7</jats:sup>). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol–SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4–9780.9); corrected<jats:italic>P</jats:italic>value = 4.7 × 10<jats:sup>–24</jats:sup>] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23–6665.26); corrected<jats:italic>P</jats:italic>value = 8.1 × 10<jats:sup>–18</jats:sup>]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol–SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.</jats:p>

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