SARS-CoV-2 Receptor ACE2 Gene Is Associated with Hypertension and Severity of COVID 19: Interaction with Sex, Obesity, and Smoking.
Adolescent
Angiotensin-Converting Enzyme 2
/ genetics
Blood Pressure
/ physiology
COVID-19
/ epidemiology
Canada
/ epidemiology
Comorbidity
Female
Genetic Predisposition to Disease
Humans
Hypertension
/ diagnosis
Male
Middle Aged
Obesity
/ diagnosis
Polymorphism, Single Nucleotide
SARS-CoV-2
/ physiology
Severity of Illness Index
Sex Factors
Smoking
/ epidemiology
ACE2
COVID-19
SARS–CoV-2
blood pressure
hypertension
obesity
sex
smoking
Journal
American journal of hypertension
ISSN: 1941-7225
Titre abrégé: Am J Hypertens
Pays: United States
ID NLM: 8803676
Informations de publication
Date de publication:
20 04 2021
20 04 2021
Historique:
received:
15
07
2020
revised:
09
11
2020
accepted:
31
12
2020
pubmed:
3
1
2021
medline:
6
5
2021
entrez:
2
1
2021
Statut:
ppublish
Résumé
Angiotensin-converting enzyme 2 (ACE2) has been identified as the entry receptor for coronaviruses into human cells, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). Since hypertension (HT) is a leading comorbidity in non-survivors of COVID-19, we tested for association between ACE2 gene and HT in interaction with specific pre-existing conditions known to be associated with COVID-19 severity. Genetic analysis of ACE2 gene was conducted in French-Canadian (FC) and British populations. In FC individuals, the T allele of the single nucleotide polymorphism rs2074192 of ACE2 gene was a risk factor for HT in adult obese males [odds ratio (OR) = 1.39, 95% confidence interval (CI) 1.06-1.83)] and even more so in obese males who smoked (OR = 1.67, CI: 1.24-2.55), but not in lean males, non-smoker males or females. The T allele was significantly associated with severity of HT and with earlier penetrance of HT in obese smoking males. Significant interaction between the T allele and obesity was present in both sexes. The association of ACE2 (rs233575) genotype with blood pressure was also seen in adolescents but the interaction with obesity was present only in females. Several variants in ACE2 gene were found to be associated with HT in obese, smoking males in British individuals of the UK Biobank. In addition, we observed more severe outcomes to COVID-19 in association with ACE2 risk alleles in obese, smoking males. This is the first report that ACE2 variants are associated with earlier penetrance and more severe HT and with more severe outcomes of COVID-19 in obese smoking males.
Sections du résumé
BACKGROUND
Angiotensin-converting enzyme 2 (ACE2) has been identified as the entry receptor for coronaviruses into human cells, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). Since hypertension (HT) is a leading comorbidity in non-survivors of COVID-19, we tested for association between ACE2 gene and HT in interaction with specific pre-existing conditions known to be associated with COVID-19 severity.
METHODS
Genetic analysis of ACE2 gene was conducted in French-Canadian (FC) and British populations.
RESULTS
In FC individuals, the T allele of the single nucleotide polymorphism rs2074192 of ACE2 gene was a risk factor for HT in adult obese males [odds ratio (OR) = 1.39, 95% confidence interval (CI) 1.06-1.83)] and even more so in obese males who smoked (OR = 1.67, CI: 1.24-2.55), but not in lean males, non-smoker males or females. The T allele was significantly associated with severity of HT and with earlier penetrance of HT in obese smoking males. Significant interaction between the T allele and obesity was present in both sexes. The association of ACE2 (rs233575) genotype with blood pressure was also seen in adolescents but the interaction with obesity was present only in females. Several variants in ACE2 gene were found to be associated with HT in obese, smoking males in British individuals of the UK Biobank. In addition, we observed more severe outcomes to COVID-19 in association with ACE2 risk alleles in obese, smoking males.
CONCLUSIONS
This is the first report that ACE2 variants are associated with earlier penetrance and more severe HT and with more severe outcomes of COVID-19 in obese smoking males.
Identifiants
pubmed: 33386398
pii: 6056793
doi: 10.1093/ajh/hpaa223
pmc: PMC7799248
doi:
Substances chimiques
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
367-376Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : P50 HL054998
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.
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