Association of DIO2 and MCT10 Polymorphisms with Persistent Symptoms in LT4-Treated Patients in UK Biobank.

Abstract

BACKGROUND:

Some evidence suggests gene-treatment interactions might cause persistent symptoms in individuals receiving levothyroxine (LT4) treatment. We investigated, as previously hypothesized, if single nucleotide polymorphisms (SNPs) in rs225014 (Thr92Ala), rs225015, or rs12885300 (ORFa-Gly3Asp) in the Deiodinase 2 gene (DIO2), or rs17606253 in the Monocarboxylate Transporter 10 gene (MCT10) were associated with outcomes indicative of local tissue hypothyroidism in LT4-treated patients and controls.

METHODS:

We included 18,761 LT4-treated patients and 360,534 controls in a population-based cross-sectional study in UK Biobank. LT4 treatment was defined as a diagnosis of hypothyroidism and self-reported use of LT4 without use of T3. Outcomes were psychological well-being, cognitive function, and cardiovascular risk factors. Associations were evaluated by linear, logistic, or ordinal logistic multiple regression. Adjustments included sex, age, sex-age interaction, and genetic principal components 1-10.

RESULTS:

Compared to controls, LT4 treatment was adversely associated with almost all outcomes, most noteworthy: Increased frequency of tiredness (p < 0.001), decreased well-being factor score (p < 0.001), increased reaction-time (p < 0.001), and increased BMI (p < 0.001). Except for a significant association between the minor rs225015 A allele and financial dissatisfaction, there was no association of rs225014, rs225015, rs12885300, or rs17606253 with any outcomes in LT4-treated patients. For all outcomes, carrying the risk allele at these four SNPs did not amplify symptoms associated with LT4 treatment compared to controls.

CONCLUSIONS:

rs225014, rs225015, rs12885300, and rs17606253 could not explain changed psychological well-being, cognitive function, or cardiovascular risk factors in LT4-treated patients. Our findings do not support a gene-treatment interaction between these SNPs and LT4 treatment.

• Authors: Christian Zinck Jensen, Jonas Lynggaard Isaksen, Gustav Ahlberg, Morten Salling Olesen, Birte Nygaard, Christina Ellervik, Jørgen Kim Kanters
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) (Sep 22 2023) ISSN: 1945-7197 [Electronic] United States
• PMID: 37740545 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].