Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank
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Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank. / Jensen, Christian Zinck; Isaksen, Jonas Lynggaard; Ahlberg, Gustav; Olesen, Morten Salling; Nygaard, Birte; Ellervik, Christina; Kanters, Jørgen Kim.
In: The Journal of clinical endocrinology and metabolism, Vol. 109, No. 2, 2024, p. e613-e622.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank
AU - Jensen, Christian Zinck
AU - Isaksen, Jonas Lynggaard
AU - Ahlberg, Gustav
AU - Olesen, Morten Salling
AU - Nygaard, Birte
AU - Ellervik, Christina
AU - Kanters, Jørgen Kim
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2024
Y1 - 2024
N2 - CONTEXT: Some evidence suggests gene-treatment interactions might cause persistent symptoms in individuals receiving levothyroxine (LT4) treatment.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.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.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.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.
AB - CONTEXT: Some evidence suggests gene-treatment interactions might cause persistent symptoms in individuals receiving levothyroxine (LT4) treatment.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.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.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.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.
KW - Humans
KW - Thyroxine/therapeutic use
KW - Iodide Peroxidase/genetics
KW - Iodothyronine Deiodinase Type II
KW - UK Biobank
KW - Biological Specimen Banks
KW - Cross-Sectional Studies
KW - Hypothyroidism/drug therapy
KW - Polymorphism, Single Nucleotide
U2 - 10.1210/clinem/dgad556
DO - 10.1210/clinem/dgad556
M3 - Journal article
C2 - 37740545
VL - 109
SP - e613-e622
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -
ID: 386610020