<p>This study investigated the role of Angiotensin-Converting Enzyme 2 (ACE2) gene polymorphisms in Corona Virus Disease of 2019 (COVID-19) pathogenesis by comparing Intensive Care Unit (ICU) patients and outpatients. The study included 299 COVID-19 patients, with 199 outpatients (control group) and 100 ICU patients (case group). ACE2 polymorphisms were assessed using Polymerase Chain Reaction (PCR) and High Resolution Melting analysis (HRM), and confirmed via Sanger sequencing. Three-dimensional structures of mutant proteins were simulated and compared. The age distribution among the case group (29 to 75&#xa0;years old, median 53, IQR = 44–72) and control group (14 to 68&#xa0;years old, median 39, IQR = 31–60) did not show significant differences between men and women in either group (<i>p-value</i> = <b>0.616</b>). However, men were 2.54 times more likely to be admitted to the ICU (p = <b>0.032</b>). ICU patients had a significantly higher prevalence of medical history compared to outpatients (p &lt; <b>0.001</b>) and were 3.45 times more likely to be admitted to the ICU (p = <b>0.000</b>). Clinical manifestations such as fever, cough, dyspnea, chest pain, headache, rhinorrhea, and myalgia showed significant differences between the case and control groups (<i>p-value</i> &gt; <b>0.05</b>). Certain outcomes, including diabetes (<i>p-value</i> = <b>0.015</b>), cough (<i>p-value</i> = <b>0.000</b>), dyspnea (<i>p-value</i> = <b>0.000</b>), and chest pain (<i>p-value</i> = <b>0.010</b>), were significantly associated with ICU hospitalization. No significant differences in ACE2 gene mutations were found between the case and control groups (p &gt; <b>0.050</b>). Identified mutations included rs771621249, rs1928150510, rs751484521, rs41303171, rs35803318, and three new Single Nucleotide Polymorphisms (SNPs). Logistic regression and haplotype analysis of SNPs in exons 1 and 17 showed no significant associations with ICU admission. Allele frequencies were compared with the 1000 Genomes Project, revealing minor variations across populations. The Root-Mean-Square Deviation (RMSD) of carbon-α for Asn58Lys and Ala59Val mutants were 0.204 and 0.0189, respectively.This study revealed significant differences in gender, clinical manifestations, and medical history between ICU patients and outpatients with COVID-19. However, no significant differences were observed in ACE2 gene mutations between the two groups. The identified mutations and their corresponding structural changes warrant further investigation to better understand their potential implications in COVID-19 pathogenesis.</p>

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ACE2 gene polymorphisms and medical implications in COVID-19: a comparative study between intensive care unit (ICU) and outpatient settings

  • Nooshin Hasheminia,
  • Sabah Hassani,
  • Fariba Ebrahimi,
  • Nasrin Moghimi,
  • Arash Pooladi,
  • Khaled Rahmani,
  • Pardis Mohammadzadeh,
  • Yousef Moradi,
  • Sherko Nasseri

摘要

This study investigated the role of Angiotensin-Converting Enzyme 2 (ACE2) gene polymorphisms in Corona Virus Disease of 2019 (COVID-19) pathogenesis by comparing Intensive Care Unit (ICU) patients and outpatients. The study included 299 COVID-19 patients, with 199 outpatients (control group) and 100 ICU patients (case group). ACE2 polymorphisms were assessed using Polymerase Chain Reaction (PCR) and High Resolution Melting analysis (HRM), and confirmed via Sanger sequencing. Three-dimensional structures of mutant proteins were simulated and compared. The age distribution among the case group (29 to 75 years old, median 53, IQR = 44–72) and control group (14 to 68 years old, median 39, IQR = 31–60) did not show significant differences between men and women in either group (p-value = 0.616). However, men were 2.54 times more likely to be admitted to the ICU (p = 0.032). ICU patients had a significantly higher prevalence of medical history compared to outpatients (p < 0.001) and were 3.45 times more likely to be admitted to the ICU (p = 0.000). Clinical manifestations such as fever, cough, dyspnea, chest pain, headache, rhinorrhea, and myalgia showed significant differences between the case and control groups (p-value > 0.05). Certain outcomes, including diabetes (p-value = 0.015), cough (p-value = 0.000), dyspnea (p-value = 0.000), and chest pain (p-value = 0.010), were significantly associated with ICU hospitalization. No significant differences in ACE2 gene mutations were found between the case and control groups (p > 0.050). Identified mutations included rs771621249, rs1928150510, rs751484521, rs41303171, rs35803318, and three new Single Nucleotide Polymorphisms (SNPs). Logistic regression and haplotype analysis of SNPs in exons 1 and 17 showed no significant associations with ICU admission. Allele frequencies were compared with the 1000 Genomes Project, revealing minor variations across populations. The Root-Mean-Square Deviation (RMSD) of carbon-α for Asn58Lys and Ala59Val mutants were 0.204 and 0.0189, respectively.This study revealed significant differences in gender, clinical manifestations, and medical history between ICU patients and outpatients with COVID-19. However, no significant differences were observed in ACE2 gene mutations between the two groups. The identified mutations and their corresponding structural changes warrant further investigation to better understand their potential implications in COVID-19 pathogenesis.