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Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study.

Publication ,  Journal Article
Chen, P-L; Shih, S-R; Wang, P-W; Lin, Y-C; Chu, C-C; Lin, J-H; Chen, S-C; Chang, C-C; Huang, T-S; Tsai, KS; Tseng, F-Y; Wang, C-Y; Lu, J-Y ...
Published in: Nat Commun
July 7, 2015

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*38:02 (Armitage trend Pcombined=6.75 × 10(-32)) and HLA-DRB1*08:03 (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*38:02 and HLA-DRB1*08:03 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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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 7, 2015

Volume

6

Start / End Page

7633

Location

England

Related Subject Headings

  • Odds Ratio
  • Humans
  • HLA-DRB1 Chains
  • HLA-B Antigens
  • HLA Antigens
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Antithyroid Agents
  • Agranulocytosis
 

Citation

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Chen, P.-L., Shih, S.-R., Wang, P.-W., Lin, Y.-C., Chu, C.-C., Lin, J.-H., … Chang, T.-C. (2015). Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat Commun, 6, 7633. https://doi.org/10.1038/ncomms8633
Chen, Pei-Lung, Shyang-Rong Shih, Pei-Wen Wang, Ying-Chao Lin, Chen-Chung Chu, Jung-Hsin Lin, Szu-Chi Chen, et al. “Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study.Nat Commun 6 (July 7, 2015): 7633. https://doi.org/10.1038/ncomms8633.
Chen P-L, Shih S-R, Wang P-W, Lin Y-C, Chu C-C, Lin J-H, et al. Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat Commun. 2015 Jul 7;6:7633.
Chen, Pei-Lung, et al. “Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study.Nat Commun, vol. 6, July 2015, p. 7633. Pubmed, doi:10.1038/ncomms8633.
Chen P-L, Shih S-R, Wang P-W, Lin Y-C, Chu C-C, Lin J-H, Chen S-C, Chang C-C, Huang T-S, Tsai KS, Tseng F-Y, Wang C-Y, Lu J-Y, Chiu W-Y, Chen Y-H, Chen Y-T, Fann CS-J, Yang W-S, Chang T-C. Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat Commun. 2015 Jul 7;6:7633.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 7, 2015

Volume

6

Start / End Page

7633

Location

England

Related Subject Headings

  • Odds Ratio
  • Humans
  • HLA-DRB1 Chains
  • HLA-B Antigens
  • HLA Antigens
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Antithyroid Agents
  • Agranulocytosis