| Title: | Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank |
| Journal: | The Journal of Clinical Endocrinology & Metabolism |
| Published: | 22 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37740545/ |
| DOI: | https://doi.org/10.1210/clinem/dgad556 |
Publication 9487
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Abstract
CONTEXT: Some evidence suggests gene-treatment interactions might cause persistent symptoms in individuals receiving levothyroxine (LT4) treatment.</p>
OBJECTIVE: We investigated, as previously hypothesized, if single-nucleotide variations (SNVs; formerly single-nucleotide polymorphisms) 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.</p>
METHODS: We included 18 761 LT4-treated patients and 360 534 controls in a population-based cross-sectional study in the UK Biobank. LT4 treatment was defined as a diagnosis of hypothyroidism and self-reported use of LT4 without use of 3,5,3'-triiodothyronine. 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 to 10.</p>
RESULTS: Compared to controls, LT4 treatment was adversely associated with almost all outcomes, most noteworthy: Increased frequency of tiredness (P < .001), decreased well-being factor score (P < .001), increased reaction-time (P < .001), and increased body mass index (P < .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 4 SNVs did not amplify symptoms associated with LT4 treatment compared to controls.</p>
CONCLUSION: 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 SNVs and LT4 treatment.</p>
7 Authors
- Christian Zinck Jensen
- Jonas Lynggaard Isaksen
- Gustav Ahlberg
- Morten Salling Olesen
- Birte Nygaard
- Christina Ellervik
- Jørgen Kim Kanters
1 Application
| Application ID | Title |
|---|---|
| 43247 | Genetics of complex human traits with a main focus on cardiac disease. |
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