Dataset Information

Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.

ABSTRACT:

Background and aim

Angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 and serine 11A proteases (TMPRSS2, TMPRSS11A), and a cell surface cluster of differentiation 147 (CD147) might be a gene candidate that exerts the susceptibility to and mortality from coronavirus disease 19 (COVID-19). The aim of this study was to investigate the associations between ace2, tmprss2, tmprss11a, and cd147 polymorphic variants and the severity of COVID-19 in the Ukrainian population.

Methods

The study population consisted of the Ukrainian population with COVID-19: patients without oxygen therapy (n=62), with non-invasive (n=92) and invasive (n=35) oxygen therapy, as well as control subjects (n=92). Allelic polymorphisms of ace2 rs4240157, tmprss2 rs12329760, and tmprss11a rs353163 were determined by real-time PCR, and cd147 rs8259 polymorphism was detected by PCR with subsequent restrictase analysis. We compared investigated polymorphisms distribution with other populations by meta-analysis.

Results

Our study is the first to obtain data about the distribution of investigated gene polymorphisms in the Ukrainian population: tmprss2 rs12329760 - CC 60.9%, CT 35.9%, TT 3.2%; tmprss11a rs353163 - CC 46.7%, CT 40.2%, TT 13.1%; ace2 rs4240157 - CC 7.6%, C 18.5%, CT 22.8%, TT 19.6%, T 31.5%; cd147 rs8259 - TT 60.9%, AT 32.6%, AA 6.5%. This distribution was similar to the Northern, Western and Southern European populations. There was a statistically significant difference in the frequency of tmprss2 polymorphic genotypes CC 57.1%, CT 28.6%, and TT 14.3% (P<0.05) in COVID-19 patients with invasive oxygen therapy in comparison with non-invasive oxygen therapy. This tmprss2 mutation occurs in the scavenger receptor cysteine-rich (SRCR) domain and might be important for protein-protein interaction in a calcium-dependent manner.

Conclusions

Our study indicated the presence of an association between the tmprss2 rs12329760 polymorphism and the severity of COVID-19 in the Ukrainian population.

SUBMITTER: Kaidashev I

PROVIDER: S-EPMC9987503 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.

Kaidashev Igor I Izmailova Olga O Shlykova Oksana O Kabaliei Alina A Vatsenko Anastasia A Ivashchenko Dmytro D Dudchenko Maksym M Volianskyi Andrii A Zelinskyy Gennadiy G Koval Tetiana T Dittmer Ulf U

Acta bio-medica : Atenei Parmensis 20230213 1

<h4>Background and aim</h4>Angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 and serine 11A proteases (TMPRSS2, TMPRSS11A), and a cell surface cluster of differentiation 147 (CD147) might be a gene candidate that exerts the susceptibility to and mortality from coronavirus disease 19 (COVID-19). The aim of this study was to investigate the associations between ace2, tmprss2, tmprss11a, and cd147 polymorphic variants and the severity of COVID-19 in the Ukrainian population.<h4>Methods ...[more]

PMID: 36786264

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Project description:BackgroundSince the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus' spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19.MethodThis cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760.ResultsThis study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19.ConclusionOur study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.

Dataset Information

Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.

Background and aim

Methods

Results

Conclusions

Publications

Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.

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