TY - JOUR
T1 - Heterozygote Advantage of the Type II Deiodinase Thr92Ala Polymorphism on Intrahospital Mortality of COVID-19
AU - De Lima Beltrão, Fabyan Esberard
AU - De Almeida Beltrão, Daniele Carvalhal
AU - Carvalhal, Giulia
AU - De Lima Beltrão, Fabricia Elizabeth
AU - De Souza Braga Filho, Jair
AU - De Brito Oliveira, Jocyel
AU - De Jesus, Joice Dos Santos
AU - MacHado, Gabriel Jeferson Rodríguez
AU - Dos Santos Silva, Hatilla
AU - Teixeira, Helena Mariana Pitangueira
AU - Rodrigues, Juliana Lopes
AU - De Figueiredo, Camila Alexandrina Viana
AU - Dos Santos Costa, Ryan
AU - Hecht, Fabio
AU - Bianco, Antonio C.
AU - Da Conceição Rodrigues Gonçalves, Maria
AU - Ramos, Helton Estrela
N1 - Publisher Copyright:
© 2022 The Author(s) 2022.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Context: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis. Objective: Our objectives were to evaluate were cumulative mortality during admission according to Thr92Ala-DIO2 polymorphism. Methods: Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intrahospital 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: In total, 220 consecutive patients (median age 62; 48-74 years) were stratified into 3 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%) than in Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intrahospital mortality whereas univariate and multivariate logistic regression adjusted for multiple covariates revealed a reduction that ranged from 51% to 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 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.
AB - Context: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis. Objective: Our objectives were to evaluate were cumulative mortality during admission according to Thr92Ala-DIO2 polymorphism. Methods: Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intrahospital 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: In total, 220 consecutive patients (median age 62; 48-74 years) were stratified into 3 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%) than in Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intrahospital mortality whereas univariate and multivariate logistic regression adjusted for multiple covariates revealed a reduction that ranged from 51% to 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 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.
KW - polymorphism and COVID-19
KW - thyroid
KW - type II deiodinase
UR - https://www.scopus.com/pages/publications/85130645316
UR - https://www.scopus.com/pages/publications/85130645316#tab=citedBy
U2 - 10.1210/clinem/dgac075
DO - 10.1210/clinem/dgac075
M3 - Article
C2 - 35137147
AN - SCOPUS:85130645316
SN - 0021-972X
VL - 107
SP - E2488-E2501
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -