A Polymorphism in the TMPRSS2 Gene Increases the Risk of Death in Older Patients Hospitalized with COVID-19

Clara Caldeira de Andrade; Ana Tércia Paulo Silva; Luydson Richardson Silva Vasconcelos; Pablo Rafael Silveira Oliveira; Carlos Dornels Freire de Souza; Anderson da Costa Armstrong; Rodrigo Feliciano do Carmo

doi:10.3390/v14112557

A Polymorphism in the TMPRSS2 Gene Increases the Risk of Death in Older Patients Hospitalized with COVID-19

Viruses. 2022 Nov 18;14(11):2557. doi: 10.3390/v14112557.

Authors

Clara Caldeira de Andrade¹, Ana Tércia Paulo Silva², Luydson Richardson Silva Vasconcelos³, Pablo Rafael Silveira Oliveira⁴, Carlos Dornels Freire de Souza⁵, Anderson da Costa Armstrong⁵, Rodrigo Feliciano do Carmo¹

Affiliations

¹ Post-Graduate Program in Biosciences, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina 56304-917, Brazil.
² Collegiate of Biological Sciences, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina 56304-917, Brazil.
³ Department of Parasitology, Aggeu Magalhães Institute (IAM), Recife 50740-465, Brazil.
⁴ Biology Institute, Federal University of Bahia (UFBA), Salvador 40170-115, Brazil.
⁵ Collegiate of Medicine, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina 56304-917, Brazil.

Abstract

Background: Transmembrane serine protease type 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) are the main molecules involved in the entry of SARS-CoV-2 into host cells. Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. The aim was to investigate the association between TMPRSS2 gene polymorphisms and the risk of death in hospitalized patients with COVID-19.

Methods: We included patients with confirmed COVID-19, recruited from two hospitals in northeastern Brazil from August 2020 to July 2021. Two functional polymorphisms (rs2070788 and rs12329760) in TMPRSS2 were evaluated by real-time PCR. The Kaplan-Meier method was used to estimate death. The Cox's proportional hazards model was used to adjust for potentially confounding factors.

Results: A total of 402 patients were followed prospectively. Survival analysis demonstrated that older patients carrying the rs2070788 GG genotype had shorter survival times when compared to those with AG or AA genotypes (p = 0.009). In multivariable analysis, the GG genotype was a factor independently associated with the risk of death in older individuals (hazard ratio = 4.03, 95% confidence interval 1.49 to 10.84).

Conclusions: The rs2070788 polymorphism in TMPRSS2 increases risk of death four-fold in older patients hospitalized with COVID-19.

Keywords: SARS-CoV-2; TMPRSS2; coronavirus; mortality; polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
COVID-19* / genetics
COVID-19* / mortality
Genotype
Hospitalization
Humans
Polymorphism, Single Nucleotide
SARS-CoV-2
Serine Endopeptidases* / genetics

Substances

Serine Endopeptidases
TMPRSS2 protein, human

Grants and funding

This work was supported by the Foundation for the Support of Science and Technology of the State of Pernambuco (FACEPE, acronym in Portuguese) (grant numbers APQ-0422–2.02/19 and IBPG-1384-2.02/20), by the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES, acronym in Portuguese), Finance Code 001, and by the Health Secretariat of Pernambuco (Agreement 10/2021).