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Article: HLA-B*38:02:01 Predicts Carbimazole/Methimazole-Induced Agranulocytosis

TitleHLA-B*38:02:01 Predicts Carbimazole/Methimazole-Induced Agranulocytosis
Authors
Issue Date2016
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/clpt/index.html
Citation
Clinical Pharmacology and Therapeutics, 2016 How to Cite?
AbstractThioamides 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. © 2015, The American Society for Clinical Pharmacology and Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/222448
ISSN
2015 Impact Factor: 7.268
2015 SCImago Journal Rankings: 2.414

 

DC FieldValueLanguage
dc.contributor.authorCheung, CL-
dc.contributor.authorSING, CW-
dc.contributor.authorTang, SM-
dc.contributor.authorCHENG, KF-
dc.contributor.authorPirmohamed, M-
dc.contributor.authorChoi, CH-
dc.contributor.authorHung, CS-
dc.contributor.authorLau, EY-
dc.contributor.authorLee, KF-
dc.contributor.authorMak, MW-
dc.contributor.authorLeung, JY-
dc.contributor.authorWong, TW-
dc.contributor.authorHo, AY-
dc.contributor.authorChan, KW-
dc.contributor.authorHung, VH-
dc.contributor.authorTam, V-
dc.contributor.authorSiu, SC-
dc.contributor.authorSham, PC-
dc.contributor.authorCheung, BMY-
dc.contributor.authorWong, ICK-
dc.contributor.authorTan, KCB-
dc.contributor.authorKung, AWC-
dc.date.accessioned2016-01-18T07:40:23Z-
dc.date.available2016-01-18T07:40:23Z-
dc.date.issued2016-
dc.identifier.citationClinical Pharmacology and Therapeutics, 2016-
dc.identifier.issn0009-9236-
dc.identifier.urihttp://hdl.handle.net/10722/222448-
dc.description.abstractThioamides 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. © 2015, The American Society for Clinical Pharmacology and Therapeutics.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/clpt/index.html-
dc.relation.ispartofClinical Pharmacology and Therapeutics-
dc.titleHLA-B*38:02:01 Predicts Carbimazole/Methimazole-Induced Agranulocytosis-
dc.typeArticle-
dc.identifier.emailCheung, CL: lung1212@hku.hk-
dc.identifier.emailTang, SM: claratang@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailCheung, BMY: mycheung@hkucc.hku.hk-
dc.identifier.emailWong, ICK: wongick@HKUCC-COM.hku.hk-
dc.identifier.emailTan, KCB: kcbtan@hkucc.hku.hk-
dc.identifier.emailKung, AWC: awckung@hku.hk-
dc.identifier.authorityCheung, CL=rp01749-
dc.identifier.authorityTang, SM=rp02105-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityCheung, BMY=rp01321-
dc.identifier.authorityWong, ICK=rp01480-
dc.identifier.authorityTan, KCB=rp00402-
dc.identifier.authorityKung, AWC=rp00368-
dc.identifier.doi10.1002/cpt.309-
dc.identifier.pmid26599303-
dc.identifier.scopuseid_2-s2.0-84954135540-
dc.identifier.hkuros256826-
dc.publisher.placeUnited States-

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