DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis

Olga Biakina; Yulia Mitina; Daria Gognieva; Marina Axenova; Alexandra Ermolaeva; Afina Bestavashvili; Valentin Fadeev; Abram Syrkin; Philipp Kopylov

doi:10.3390/ijms24044016

DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis

Int J Mol Sci. 2023 Feb 16;24(4):4016. doi: 10.3390/ijms24044016.

Authors

Olga Biakina¹, Yulia Mitina^{2

3}, Daria Gognieva^{1

4}, Marina Axenova⁵, Alexandra Ermolaeva⁶, Afina Bestavashvili⁴, Valentin Fadeev⁶, Abram Syrkin¹, Philipp Kopylov^{1

4}

Affiliations

¹ Department of Cardiology, Functional and Ultrasound Diagnostics of N.V. Sklifosovsky Institute for Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.
² Department of Anatomy and Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne 3010, Australia.
³ Murdoch Children's Research Institute, Melbourne 3052, Australia.
⁴ World-Class Research Center «Digital Biodesign and Personalized Healthcare», I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.
⁵ Federal State Organization "Centre for Strategic Planning and Management of Biomedical Health Risks", Ministry of Health of the Russian Federation, 119121 Moscow, Russia.
⁶ Department of Endocrinology No. 1 of N.V. Sklifosovsky Institute for Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.

Abstract

Possible triggers and genetic markers involved in pathogenesis of amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH) are currently unknown. This study aimed to analyze the association between polymorphisms in the genes involved in thyroid hormones biosynthesis and metabolism. Thirty-nine consecutive patients with confirmed type 2 amiodarone-induced thyrotoxicosis were enrolled; 39 patients on the same therapy for at least 6 months without thyroid pathology were included as a control group. A comparative study was carried out to determine the distribution and genotypes of polymorphic markers of the (Na)-iodide symporter (NIS) genes (rs7250346, C/G substitution), thyroid stimulating hormone receptor (TSHR) (rs1991517, C/G substitution), thyroid peroxidase (TPO) (rs 732609, A/C substitution), DUOX 1-1 (C/T substitution), DUOX 1-2 (G/T substitution), DUOX 1-3 (C/T substitution), glutathione peroxidase 3 (GPX3) (C/T substitution), glutathione peroxidase 4 (GPX4) (C/T substitution). Statistical analysis was performed using Prism (Version 9.0.0 (86)). This study showed that the risk of AIT2 is 3.18 times higher in the G/T of the DUOX1 gene carriers. This study is the first report of genetic markers associated with amiodarone-related adverse events conducted in humans. The obtained results indicate the necessity for a personalized approach to amiodarone administration.

Keywords: DUOX1 gene; amiodarone-induced thyrotoxicosis 2 type; genetic markers.

MeSH terms

Amiodarone* / adverse effects
Anti-Arrhythmia Agents* / adverse effects
Dual Oxidases* / genetics
Genetic Markers
Humans
Mutation, Missense
Thyrotoxicosis* / chemically induced
Thyrotoxicosis* / genetics

Substances

Amiodarone
Anti-Arrhythmia Agents
Dual Oxidases
DUOX1 protein, human
Genetic Markers

Grants and funding

This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Center ‘Digital biodesign and personalized healthcare’ № 075-15-2022-304.