Thyrotropin receptor antibodies and a genetic hint in antithyroid drug-induced adverse drug reactions
Journal
Expert Opinion on Drug Safety
Journal Volume
17
Journal Issue
8
Pages
775-784
Date Issued
2018
Author(s)
Chang C.-C.
Wang S.-H.
Chen Y.-H.
Tsai Y.-H.
Fann C.S.-J.
Abstract
Background: Antithyroid drugs (ATDs) are known to cause various adverse drug reactions (ADRs) that can lead to treatment complexity and unpredictable risks. With the aim of ensuring safer drug use, we assessed whether thyrotropin receptor antibody (TRAb) titers are associated with ATD-induced cutaneous reactions and/or hepatotoxicity, and examined potential genetic predisposition factors. Methods: We compared TRAb titers of 37 Graves’ disease (GD) patients who had experienced carbimazole/methimazole-induced cutaneous reactions and/or hepatotoxicity with those of 40 normal individuals, or 78 GD patients without the aforementioned ATD-induced ADRs. We performed a genome-wide association study and/or human leukocyte antigen genotyping on GD patients [first stage (chart reviews): 24 cases with ADRs and 423 controls; second stage (actively recruited): 45 cases with ADRs and 137 controls]. Results: For patients with Graves’ hyperthyroidism, individuals with higher TRAb titers showed a predisposition to carbimazole/methimazole-induced cutaneous reactions and/or hepatotoxicity, with an estimated odds ratio of 5.19 (cut-off value: 64%). Potential associations with the rs144542704 and rs61893841 on chromosomes 17 and 11, respectively, warrant further genetic association analysis. Conclusion: Our findings support the use of carbimazole/methimazole in patients with low TRAb titers to ensure safer drug use. The identified genetic associations warrant further research. ? 2018, ? 2018 Informa UK Limited, trading as Taylor & Francis Group.
SDGs
Other Subjects
antithyroid agent; carbimazole; HLA antigen; thiamazole; thyrotropin receptor antibody; antibody; antithyroid agent; carbimazole; thiamazole; thyrotropin receptor; adult; adverse drug reaction; aged; allele; antibody titer; Article; chromosome 11; chromosome 17; clinical article; controlled study; drug safety; female; genetic association; genetic predisposition; genome-wide association study; genotype; Graves disease; HLA system; human; jaundice; liver function test; liver toxicity; male; pruritus; side effect; single nucleotide polymorphism; skin manifestation; swelling; urticaria; adolescent; case control study; drug eruption; genetic predisposition; immunology; middle aged; toxic hepatitis; young adult; Adolescent; Adult; Aged; Antibodies; Antithyroid Agents; Carbimazole; Case-Control Studies; Chemical and Drug Induced Liver Injury; Drug Eruptions; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Graves Disease; Humans; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Young Adult
Publisher
Taylor and Francis Ltd
Type
journal article