Introduction
The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis.
Methods
Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intra-hospital mortality from COVID-19 in adult patients admitted between June and August 2020. Blood biochemistry, thyroid function tests, length of stay, comorbidities, complications, and severity scores were also studied according to Thr92Ala-DIO2 polymorphism.
Results
220 consecutive patients [median age: 62 (48–74) years] were stratified into three subgroups: Thr/Thr (n=79), Thr/Ala (n=119) and Ala/Ala (n=23). While the overall mortality was 17.3%, the lethality was lower in Ala/Thr patients (12.6%) when compared to Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intra-hospital mortality whereas the univariate and multivariate logistic regression adjusted for multiple covariates, revealed a reduction that ranged from 51-66%. The association of the Thr/Ala genotype with better clinical outcomes was confirmed in a metanalysis of 5 studies, including the present one.
Conclusion
Here we provide evidence for a protective role played by the Thr92Ala-DIO2 heterozygosity in patients with COVID-19. This protective effect follows an inheritance model known as overdominance, in which the phenotype of the heterozygote lies outside the phenotypical range of both homozygous.
ObjectiveThis study aimed to evaluate the effect of genetic variants in glutamate ionotropic receptor N-methyl-d-aspartate type subunit 2B (GRIN2B), glutamate ionotropic receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type subunit 1 (GRIA1), and brain-derived neurotrophic factor (BDNF) genes on therapeutic response, remission, and total Montgomery-Åsberg Depression Rating Scale scores after treatment with ketamine or esketamine in treatment-resistant depression (TRD) patients.MethodsParticipants (N = 60) are from a double-blind, randomized, noninferiority clinical trial comparing single-dose intravenous ketamine (0.5 mg/kg) to esketamine (0.25 mg/kg) for TRD. Montgomery-Åsberg Depression Rating Scale was applied at baseline, 24 hours, 72 hours, and 7 days postinfusion to assess depressive symptoms. Blood samples were collected to evaluate single nucleotide polymorphisms rs1805502 (GRIN2B), rs1994862 (GRIA1), and rs6265 (BDNF).ResultsThere was no association between rs1805502, rs1994862, or rs6265 polymorphisms and antidepressant response (P = 0.909, P = 0.776, and P = 0.482, respectively), remission P = 0.790, P = 0.086, and P = 0.669), or Montgomery-Åsberg Depression Rating Scale scores at each time point (P = 0.907, P = 0.552, and P = 0.778).ConclusionsWe found no association between the studied single nucleotide polymorphisms (rs6265, rs1805502, and rs1994862) and ketamine's therapeutic action in TRD patients. Further studies with larger samples are needed to clarify the utility of these genes of interest as predictors for antidepressant treatment.
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