| Literature DB >> 26599303 |
C-L Cheung1,2,3,4, C-W Sing1, C S M Tang4,5, V K F Cheng1, M Pirmohamed6,7, C-H Choi8, C-S Hung9, E Y-F Lau10, K F Lee11, M W-H Mak11, J Y Y Leung12, T-W Wong12, A Y Y Ho13, K-W Chan14, Vhf Hung14, V Tam15, S-C Siu16, H-K Pang10, W Z-M Wat10, H H-Y Lee10, C-T Chung10, R S-M Hue10, P-C Sham4,5, B M Y Cheung2,3,4, I C K Wong1,2,17, K C B Tan3, A W C Kung3.
Abstract
Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.Entities:
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Year: 2016 PMID： 26599303 DOI： 10.1002/cpt.309
Source DB: PubMed Journal: Clin Pharmacol Ther ISSN： 0009-9236 Impact factor: 6.875