Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study.
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| 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*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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| Authors | Pei-Lung Chen, Shyang-Rong Shih, Pei-Wen Wang, Ying-Chao Lin, Chen-Chung Chu, Jung-Hsin Lin, Szu-Chi Chen, Ching-Chung Chang, Tien-Shang Huang, Keh Sung Tsai, Fen-Yu Tseng, Chih-Yuan Wang, Jin-Ying Lu, Wei-Yih Chiu, Chien-Ching Chang, Yu-Hsuan Chen, Yuan-Tsong Chen, Cathy Shen-Jang Fann, Wei-Shiung Yang, Tien-Chun Chang |
| Journal | Nature communications (Nat Commun) Vol. 6 Pg. 7633 (Jul 07 2015) ISSN: 2041-1723 [Electronic] England |
| PMID | 26151496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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