Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality

Background: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptor...

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Autores principales:	Mohammad Muzaffar Mir, Rashid Mir, Mushabab Ayed Abdullah Alghamdi, Badr Abdulmohsin Alsayed, Javed Iqbal Wani, Muffarah Hamid Alharthi, Abdullah M. AL-Shahrani
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	gene polymorphism infection SARS-CoV-2 COVID-19 pathogenesis ACE1-angiotensin-converting enzyme 1 Medicine R
Acceso en línea:	https://doaj.org/article/f52639dcefd44b4eaae09b177fb6e1a4
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id	oai:doaj.org-article:f52639dcefd44b4eaae09b177fb6e1a4
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	gene polymorphism infection SARS-CoV-2 COVID-19 pathogenesis ACE1-angiotensin-converting enzyme 1 Medicine R
spellingShingle	gene polymorphism infection SARS-CoV-2 COVID-19 pathogenesis ACE1-angiotensin-converting enzyme 1 Medicine R Mohammad Muzaffar Mir Rashid Mir Mushabab Ayed Abdullah Alghamdi Badr Abdulmohsin Alsayed Javed Iqbal Wani Muffarah Hamid Alharthi Abdullah M. AL-Shahrani Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality
description	Background: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality. Methodology: This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping. Results: Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms (<i>p</i> < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (<i>p</i>-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19–4.70), RR = 1.39 (1.09–1.77), <i>p</i> < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08–4.46), <i>p</i> < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11–2.27), RR 1.21 (1.05–1.41) <i>p</i> < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age (<i>p</i> < 0.035), T2D (<i>p</i> < 0.0013), hypertension (<i>p</i> < 0.0031) and coronary artery disease (<i>p</i> < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), <i>p</i> < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), <i>p</i> < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls (<i>p</i> < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2–CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92–3.99), <i>p</i> < 0.010 and also ACE2–CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53–4.62), <i>p</i> < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender (<i>p</i> < 0.04), T2D (<i>p</i> < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), <i>p</i> < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761–3.45), <i>p</i> < 0.010. Conclusions: It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2–CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.
format	article
author	Mohammad Muzaffar Mir Rashid Mir Mushabab Ayed Abdullah Alghamdi Badr Abdulmohsin Alsayed Javed Iqbal Wani Muffarah Hamid Alharthi Abdullah M. AL-Shahrani
author_facet	Mohammad Muzaffar Mir Rashid Mir Mushabab Ayed Abdullah Alghamdi Badr Abdulmohsin Alsayed Javed Iqbal Wani Muffarah Hamid Alharthi Abdullah M. AL-Shahrani
author_sort	Mohammad Muzaffar Mir
title	Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality
title_short	Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality
title_full	Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality
title_fullStr	Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality
title_full_unstemmed	Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality
title_sort	strong association of angiotensin converting enzyme-2 gene insertion/deletion polymorphism with susceptibility to sars-cov-2, hypertension, coronary artery disease and covid-19 disease mortality
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f52639dcefd44b4eaae09b177fb6e1a4
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spelling	oai:doaj.org-article:f52639dcefd44b4eaae09b177fb6e1a42021-11-25T18:07:09ZStrong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality10.3390/jpm111110982075-4426https://doaj.org/article/f52639dcefd44b4eaae09b177fb6e1a42021-10-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1098https://doaj.org/toc/2075-4426Background: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality. Methodology: This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping. Results: Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms (<i>p</i> < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (<i>p</i>-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19–4.70), RR = 1.39 (1.09–1.77), <i>p</i> < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08–4.46), <i>p</i> < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11–2.27), RR 1.21 (1.05–1.41) <i>p</i> < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age (<i>p</i> < 0.035), T2D (<i>p</i> < 0.0013), hypertension (<i>p</i> < 0.0031) and coronary artery disease (<i>p</i> < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), <i>p</i> < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), <i>p</i> < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls (<i>p</i> < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2–CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92–3.99), <i>p</i> < 0.010 and also ACE2–CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53–4.62), <i>p</i> < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender (<i>p</i> < 0.04), T2D (<i>p</i> < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), <i>p</i> < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761–3.45), <i>p</i> < 0.010. Conclusions: It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2–CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.Mohammad Muzaffar MirRashid MirMushabab Ayed Abdullah AlghamdiBadr Abdulmohsin AlsayedJaved Iqbal WaniMuffarah Hamid AlharthiAbdullah M. AL-ShahraniMDPI AGarticlegene polymorphisminfectionSARS-CoV-2COVID-19pathogenesisACE1-angiotensin-converting enzyme 1MedicineRENJournal of Personalized Medicine, Vol 11, Iss 1098, p 1098 (2021)

Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality

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