Heterozygote advantage of the type II deiodinase thr92Ala polymorphism on intrahospital mortality of COVID-19
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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.
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The Thr92Ala polymorphism has been shown to be beneficial in the general population: heterozygosity reduces acute lung injury in sepsis by 35% and reduces mortality from COVID-19 by 50%.
“This polymorphism has been shown to be beneficial in the general population (heterozygosity reduces acute lung injury in sepsis by 35% and reduces mortality from COVID-19 by 50%) (39, 40).”
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Bashir, K. (2025) · Endocrine Research · doi:10.1080/07435800.2025.2562007
- Authors
- de Lima Beltrão, F. E., de Almeida Beltrão, D. C., Carvalhal, G., de Lima Beltrão, F. E., de Souza Braga Filho, J., de Brito Oliveira, J., de Jesus, J. D. S., Machado, G. J. R., dos Santos Silva, H., Teixeira, H. M. P., Rodrigues, J. L., de Figueiredo, C. A. V., dos Santos Costa, R., Hecht, F., Bianco, A. C., da Conceição Rodrigues Gonçalves, M., & Ramos, H. E.
- Affiliations
- Lauro Wanderley University Hospital, Federal University of Paraíba, João Pessoa, Paraíba, Brazil
- University Center of João Pessoa – UNIPE, João Pessoa, PB, Brazil
- Universidade Federal de Campina Grande (BR)
- Bioregulation Department, Health and Science Institut, Federal University of Bahia, Salvador, Bahia, Brazil
- Universidade Federal da Bahia (BR)
- Laboratory of Immunopharmacology and Molecular Biology, Health Sciences Institute, Federal University of Bahia, Brazil
- The Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- University of Chicago (US)
- Post-Graduation Program in Nutritional Sciences, Department of Nutrition, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil
- Corresponding author
- Ramos, Helton Estrela
- ORCID
- de Lima Beltrão, Fabyan Esberard
- de Almeida Beltrão, Daniele Carvalhal
- Carvalhal, Giulia
- de Lima Beltrão, Fabricia Elizabeth
- de Souza Braga Filho, Jair
- de Brito Oliveira, Jocyel
- de Jesus, Joice dos Santos
- Machado, Gabriel Jeferson Rodríguez
- dos Santos Silva, Hatilla
- Teixeira, Helena Mariana Pitangueira
- Rodrigues, Juliana Lopes
- de Figueiredo, Camila Alexandrina Viana
- dos Santos Costa, Ryan
- Hecht, Fabio
- Bianco, Antonio C
- da Conceição Rodrigues Gonçalves, Maria
- Ramos, Helton Estrela
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2022-02-09
- Volume
- 107
- Issue
- 6
- Pages
- e2488-e2501
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC8903419
- OpenAlex
- W4211020255
- Cited by
- 12
- References
- 66
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065055)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- type 2 deiodinase, DIO2, COVID-19 pandemic, in-hospital mortality, overdominance, genetic susceptibility, thyroid hormone metabolism, SARS-CoV-2
- MeSH terms
- COVID-19, Iodothyronine Deiodinase Type II, Heterozygote, Humans, Iodide Peroxidase, Longitudinal Studies, Prospective Studies, Hospital Mortality, Polymorphism, Single Nucleotide
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