Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank

被引：1

作者：

Jensen, Christian Zinck ^{[1
,2
]}

Isaksen, Jonas Lynggaard ^{[1
]}

Ahlberg, Gustav ^{[3
,4
]}

Olesen, Morten Salling ^{[3
,4
]}

Nygaard, Birte ^{[2
,5
]}

Ellervik, Christina ^{[5
,6
]}

Kanters, Jorgen Kim ^{[1
,7
]}

机构：

[1] Univ Copenhagen, Dept Biomed Sci, Lab Expt Cardiol, DK-2200 Copenhagen, Denmark

[2] Copenhagen Univ Hosp Herlev & Gentofte, Ctr Endocrinol & Metab, Borgmester Ib Juuls Vej 1, DK-2730 Herlev, Denmark

[3] Copenhagen Univ Hosp, Rigshosp, Heart Ctr, Lab Mol Cardiol,Dept Cardiol, DK-2100 Copenhagen, Denmark

[4] Univ Copenhagen, Dept Biomed Sci, DK-2200 Copenhagen, Denmark

[5] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark

[6] Harvard Med Sch, Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA

[7] Univ Calif San Francisco, Ctr Physiol Res, San Francisco, CA 94131 USA

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2024年 / 109卷 / 02期

关键词：

rs225014; rs225015; rs12885300; rs17606253; DIO2; Thr92Ala; levothyroxine; HUMAN TYPE-2 DEIODINASE; THYROID-HORMONE; UNDER-TREATMENT; HYPOTHYROIDISM; GENE; THYROXINE; THERAPY;

D O I：

10.1210/clinem/dgad556

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：e613 / e622

页数：10