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Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study.
Chen, Pei-Lung; Shih, Shyang-Rong; Wang, Pei-Wen; Lin, Ying-Chao; Chu, Chen-Chung; Lin, Jung-Hsin; Chen, Szu-Chi; Chang, Ching-Chung; Huang, Tien-Shang; Tsai, Keh Sung; Tseng, Fen-Yu; Wang, Chih-Yuan; Lu, Jin-Ying; Chiu, Wei-Yih; Chang, Chien-Ching; Chen, Yu-Hsuan; Chen, Yuan-Tsong; Fann, Cathy Shen-Jang; Yang, Wei-Shiung; Chang, Tien-Chun.
Afiliação
  • Chen PL; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Department of Medical Genetics, National Taiwan University Hospital, Taipei 100, Taiwan. [3] Graduate Institute of Medical Genomics and Proteomics, College of Me
  • Shih SR; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Department of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • Wang PW; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
  • Lin YC; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
  • Chu CC; Immunogenetics Laboratory, Department of Medical Research, Mackay Memorial Hospital, Taipei 251, Taiwan.
  • Lin JH; 1] Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. [2] School of Pharmacy, National Taiwan University, Taipei 100, Taiwan. [3] Research Center for Applied Sciences, Academia Sinica, Taipei 833, Taiwan.
  • Chen SC; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Department of Internal Medicine, New Taipei City Hospital, New Taipei 220, Taiwan.
  • Chang CC; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan. [3] Department of Internal Medicine, China Medical University, Taichung
  • Huang TS; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Department of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan. [3] Department of Social Medicine, College of Medicine, National Tai
  • Tsai KS; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [3] Department of Laboratory Medicine, College of Medicine, National
  • Tseng FY; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
  • Wang CY; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
  • Lu JY; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
  • Chiu WY; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
  • Chang CC; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
  • Chen YH; School of Pharmacy, National Taiwan University, Taipei 100, Taiwan.
  • Chen YT; 1] Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. [2] Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27708, USA.
  • Fann CS; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
  • Yang WS; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan. [3] Graduate Institute of Clinical Me
  • Chang TC; 1] Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. [2] Department of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Nat Commun ; 6: 7633, 2015 Jul 07.
Article em En | MEDLINE | ID: mdl-26151496
ABSTRACT
Graves' disease is the leading cause of hyperthyroidism affecting 1.0-1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*3802 (Armitage trend Pcombined=6.75 × 10(-32)) and HLA-DRB1*0803 (Pcombined=1.83 × 10(-9)) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13-41.48) and 6.13 (95% confidence interval=3.28-11.46), respectively. Carrying both HLA-B*3802 and HLA-DRB1*0803 increases odds ratio to 48.41 (Pcombined=3.32 × 10(-21), 95% confidence interval=21.66-108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antitireóideos / Predisposição Genética para Doença / Agranulocitose / Estudo de Associação Genômica Ampla / Genótipo / Antígenos HLA Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antitireóideos / Predisposição Genética para Doença / Agranulocitose / Estudo de Associação Genômica Ampla / Genótipo / Antígenos HLA Idioma: En Ano de publicação: 2015 Tipo de documento: Article