Details

Autor(en) / Beteiligte

• Cheung, C-L
• Sing, C-W
• Tang, CSM
• Cheng, VKF
• Pirmohamed, M
• Choi, C-H
• Hung, C-S
• Lau, EY-F
• Lee, KF
• Mak, MW-H
• Leung, JYY
• Wong, T-W
• Ho, AYY
• Chan, K-W
• Hung, VHF
• Tam, V
• Siu, S-C
• Pang, H-K
• Wat, WZ-M
• Lee, HH-Y
• Chung, C-T
• Hue, RS-M
• Sham, P-C
• Cheung, BMY
• Wong, ICK
• Tan, KCB
• Kung, AWC

Titel

HLA-B38:02:01 predicts carbimazole/methimazole-induced agranulocytosis

Ist Teil von

• Clinical pharmacology and therapeutics, 2016-05, Vol.99 (5), p.555-561

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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.