https://scholars.lib.ntu.edu.tw/handle/123456789/627670
標題: | Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study | 作者: | PEI-LUNG CHEN SHYANG-RONG SHIH Wang, Pei-Wen Lin, Ying-Chao Chu, Chen-Chung Lin, Jung-Hsin Chen, Szu-Chi CHING-CHUNG CHANG TIEN-SHANG HUANG KEH-SUNG TSAI FEN-YU TSENG CHIH-YUAN WANG JIN-YING LU WEI-YIH CHIU Chang, Chien-Ching Chen, Yu-Hsuan Chen, Yuan-Tsong Fann, Cathy Shen-Jang WEI-SHIUNG YANG TIEN-CHUN CHANG |
關鍵字: | CLOZAPINE-INDUCED AGRANULOCYTOSIS; HLA; HYPERSENSITIVITY; PHARMACOGENETICS; PREDICTION; PROGRESS; HLA-B38; SYSTEM; REGION | 公開日期: | 7-七月-2015 | 出版社: | NATURE PUBLISHING GROUP | 卷: | 6 | 期: | 1 | 來源出版物: | Nature communications | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627670 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms8633 |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。