LAUSR

Abstract Background ACE2 has been identified as the entry receptor for coronaviruses into human cells, including SARS-COV-2 that causes COVID-19. Since hypertension is a leading comorbidity in non-survivors of COVID-19, we tested for association between ACE2 gene and hypertension 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 and British populations. Results In French-Canadian individuals, the T allele of the single nucleotide polymorphism (SNP) rs2074192 of ACE2 gene was a risk factor for hypertension 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 hypertension and with earlier penetrance of hypertension 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 hypertension 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. Conclusion This is the first report that ACE2 variants are associated with earlier penetrance and more severe hypertension and with more severe outcomes of COVID-19 in obese smoking males.