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

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.

Frequency of Electrocardiographic Abnormalities in Patients With Psoriasis.

Psoriasis is a chronic inflammatory disease associated with cardiovascular disease, for example, myocardial infarction, stroke, cardiovascular death, and arrhythmias. The resting electrocardiogram may carry prognostic information, but limited evidence is available of electrocardiographic findings in subjects with psoriasis. The electrocardiographic results were compared between 1,131 subjects with self-reported psoriasis and 18,397 controls participating in the Danish General Suburban Population Study (GESUS). The mean heart rate was marginally increased in patients with psoriasis (66 ± 11 vs 65 ± 11 beats/min, p = 0.007), but not after adjustment for smoking and body mass index. All other examined electrocardiographic variables, including QT interval corrected for heart rate with the Fridericia formula, PR interval, QRS duration, R axis, P-wave duration in lead V1, P-terminal force, J point elevation in lead V1, electrocardiographic criteria for left ventricular hypertrophy, electrocardiographic signs of previous myocardial infarction, and premature ventricular or supraventricular complexes, respectively, were comparable between the 2 groups. In conclusion, psoriasis was associated with a marginal increase in resting heart rate, which was driven by smoking and increased body mass index. All other examined electrocardiographic variables were similar between the 2 groups. The results suggest that psoriasis per se is not associated with significant abnormalities of the electrocardiogram.