Association Of ACE2 Rs2074192 And Rs233574 And AGT Rs699 Gene Polymorphisms With Obesity And Disease Severity In A Cohort Of COVID-19 Affected Syrians

Since the year 2020, accumulating data identified numerous factors playing cardinal roles in inter-individual variations for COVID-19 morbidity including age, obesity, hypertension, comorbidities, in addition to genetic susceptibility. Among the key genes that might contribute to variable clinical outcomes in patients are those involved in the renin-angiotensin-aldosterone system (RAAS); namely angiotensin I and II (ACE, ACE2) and angiotensinogen (AGT). In this study, the allele and genotype frequencies of three single nucleotide polymorphisms (SNPs); ACE2 rs2074192 and rs233574 in ACE2 gene, and rs699 in AGT gene were recorded in a cohort of Syrian subjects previously suffered from COVID-19 disease with variable symptoms and comorbidities. Fifty four subjects previously inflected by COVID-19 disease were interviewed and classified based on three categories; according to blood pressure levels [normotensive (NT) or hypertensive (HT)], obesity [lean or overweight and obese (OW/OB)], and COVID-19 conditions [mild or moderate and severe (MOD/SV)].  Genotyping of the three SNPs was performed on DNA extracted from blood samples withdrawn from interviewed subjects followed by electrophoresis and DNA sequencing. We found higher allele frequencies of rs2074192 C allele, rs233574 T allele, and rs699 C allele in OW/OB females (79.2%, 45.2%, and 62.5%, respectively) compared to lean females (33.3%), p values (0.066, 0.079, and 0.043), respectively. Furthermore, the recorded association of higher allele frequencies of the three SNPs with either obesity or COVID-19 severity suggest the C allele for rs2074192, the T allele for ACE2 rs233574, and the C allele of AGT rs699 as risk factors for obesity only in female subjects and COVID-19 severity only in male subjects. Taken together, we proposed two rs2074192-rs233574-rs699 haplotypes, CC-TT-CC in females and C-T-CC in males, as risk haplotypes for COVID-19 severity in our Syrian cohort. Further studies with larger number of COVID-19 affected Syrian subjects should be performed to confirm our preliminary results.