Association of the AGT rs699 and ACE rs1799752 Gene Polymorphisms with Obesity and COVID-19 Severity in a Cohort of Syrian Patients

Abstract

Background and Aim: The COVID-19 pandemic represents a sound example of inter-individual variations in disease severity ranging from asymptomatic and mild disease to severe illness, which may end up with organ failure and ultimately death. The genetic basis of the inter-individual disparities in disease severity is an area of rigorous research worldwide. This study aimed at investigating the proposed associations between disease severity and two gene polymorphisms, namely the rs699 in angiotensinogen (AGT) gene and the rs1799752 in the angiotensin converting enzyme 1 (ACE I) gene, due to the key regulatory roles of the encoded proteins in the Renin-Angiotensin-Aldosterone System (RAAS), and their linkage to risk factors (i.e., hypertension and obesity).

Study Subjects and Methods: We interviewed 54 subjects who had been previously diagnosed with COVID-19. Information on demographics, COVID-19 severity and comorbidities were collected. Patients were classified based on body mass index (BMI) into three categories; lean or normal weight (NW), overweight (OW), and obese (OB), and graded based on COVID-19 severity into mild, moderate and severe disease. Whole blood samples were drawn and genotyping was performed via electrophoresis (rs1799752) or standard sequencing (rs699) of the specific polymerase chain reactions (PCR) amplicons.

Results: Our findings revealed a higher frequency (41.2%) of the rs1799752 (I) allele in the OW and OB groups compared with the NW subjects (20%) (p= 0.024). The difference was more evident when limiting comparison to young (< 50 years) OW and OB versus NW individuals (50% versus 13.9%, respectively) (p= 0.0012). Females had higher frequency (70.8%) of the TC genotype and only (12.5%) of the CC, whereas males had disparate frequencies of (33.3%) and (40%), respectively (p= 0.018). The ID genotype was dominant (62.5%) whereas the DD genotype made only (18.75%) of the youth (< 50 years) in the OW and OB groups, compared with frequencies of (27.8%) and (72.2%), respectively, in the NW individuals (p= 0.012). Furthermore, the ID and DD genotypes constituted (50.0% and 41.2%), respectively, of the moderate and severe cases versus (35.0% and 50.0%), respectively, in the mild COVID-19 patients (p= 0.04). Eleven of the 34 (32.35%) moderate and severe cases of the TC-ID haplotype compared with only two cases of 20 (10.00%) in the group of mild disease. Conclusions: Our results suggest correlations between the I allele and ID genotype with obesity, and ID genotype and TC-ID haplotype with the COVID-19 severity in a cohort of Syrian patients.