تعدد الأشكال الجينية لمستوى الإنزيم المحول للأنجيوتنسين -2 ومستقبلاته وعلاقتها بخطورة جائحة كوفيد -19 من العراقيين

Genetic Polymorphism of Angiotensin Converting Enzyme-2 level and Receptors in Relation to Severity of Iraqi COVID-19 Pandemic

Abstract

Coronavirus (Covid-19) is clustered under the viral family group that causes disease in mammals and birds. A pandemic novel coronavirus was named as ‘‘Corona Virus Disease 2019’’ by World Health Organization (WHO) in Geneva, Switzerland. This is the deadly third-generation virus in Corona family preceded by Middle East Respiratory Syndrome (MERS) in 2012 and Severe Acute Respiratory Syndrome (SARS) in 2003. The incidence of SARS-CoV-2 infection is seen most often in adult male patients with the median age of the patients was between 34 and 59 years. SARS-CoV-2 is also more likely to infect people with chronic comorbidities such as cardiovascular and, hypertension and diabetes. The highest proportion of severe cases occurs in adults ≥60 years of age.
Angiotensin converting enzyme-2 (ACE-2) is a protein on the surface of many cell types. It is an enzyme that generates small proteins – by cutting up the larger protein angiotensinogen – that then go on to regulate functions in the cell. Using the spike-like protein on its surface, the SARS-CoV-2 virus binds to ACE2 – like a key being inserted into a lock – prior to entry and infection of cells. Hence, ACE2 acts as a cellular doorway – a receptor – for the virus that causes covid-19. ACE2 acts as the receptor for the SARS-CoV-2 virus and allows it to infect the cell.
The quantity of receptors determine whether someone gets more or less sick, because the SARS-CoV-2 virus requires ACE2 to infect cells but the precise relationship between ACE2 levels, viral infectivity and severity of infection .
The aim of the presented project is to study the association between various biomarkers including angiotensin-converting enzyme and its receptor gene polymorphism with severity of covid-19 infection in Iraqi pandemic of Kerbala province.
This study was conducted on 176 subjects which diagnosed by physician and were divided into three groups: 59 of them were with severe infected covid-19, 54 of them were with moderate infected covid-19 and 63 of them were apparently healthy control who’s attended the hospital for checkup. Severe and moderate patients were collected from Al-Hussein Teaching Hospital, Al-Hussein Medical City, Kerbala Health Directorates, Kerbala – Iraq during April, 2020- March, 2021 with matched age ranged between (23-88) years. Genomic DNA was extracted from blood then genotyping of ACE-2 receptor by using special primers was investigated using polymerase chain reaction.
The anthropometric and biomarkers determined included: Age, Body mass index, Ferritin, Lactate dehydrogenase (LDH) Level , C-reactive protein (CRP), Aniotensin converting enzyme-2 (ACE-2) Level , Alanine aminotransferase (ALT) Level , Aspartate aminotransferase (AST) Level and Alkaline phosphatase (ALP) level .
The genotype of ACE -2 obtained in all of 176 samples of the presented study (severe, moderate and control) indicate that three types of allele were observed:
1. ACE-1 deletion/deletion polymorphisms (D/D)
2. ACE-1 insertion/deletion polymorphisms (I/D)
3. ACE-1 insertion/insertion polymorphism (I/I))
Every patients carry (D/D) they were severely infection and increased in ACE- 2 enzyme, but the patients that carry (I/D), (I/I) they were moderate infection with covid -19. The ACE-2 gene polymorphism and ACE-2 activity levels were associated with the severity of covid-19. The three selected groups were found to be different with respect to Ferritin, LDH, CRP, ACE, ALT, AST and ALK .The mean values of the variables Ferritin ,LDH,CRP,ACE,ALT,AST and ALK are significantly higher in the sever and moderate compared to that of healthy control .
In conclusion, the data observed indicated that if those control groups will be infected with covid-19, they considered as severe cases due to that the D-allele is associated with higher ACE-2 expresion ; therefore, patients that carry D-allele, especially those with the D/D genotype, are at higher risk of pulmonary morbidity and/or mortality .