Immunogenetic Study of IL-12 and ACE-2 Genes Polymorphism among Patients with COVID-19
نور سلمان كاظم, هدى كاظم حسن حسب
كلية العلوم-جامعة بابل · العراق
The acute respiratory syndrome caused by the Coronavirus, which is one of the respiratory viruses that spread quickly, swept the world and killed more than six million people. This led to the creation of many vaccines and medicines in record time to lessen the severity of this disease and speed up the healing of patients. This study looks at the genetic heterogeneity of angiotensin-converting enzyme-2 (ACE-2) and interleukin-12 (IL-12) in patients with COVID-19 and compares these cytokines and receptors between severe and non-severe cases. This sectional-cross study included 100 blood specimens from COVID-19 patients with ages ranging from 15 to 80 years, distributed according to the severity of disease as follows: 46 severe and 54 non-severe, who had been hospitalized at the COVID-19 wards in Merjan Medical City and Imam Sadiq Hospital in Babylon Province for 2 months (November and December 2021). Two parts of the work were conducted: the first was an immunological study for the evaluation of serum IL-12 and ACE-2, and the second was a genetic study for the detection of genetic polymorphisms of ACE-2, IL-12A, and IL-12B. Results reveal that the serum levels of both ACE-2 and IL-12 were measured in COVID-19 patients, and the results were compared using an independent T-test. It was found that IL-12 levels revealed a significant difference (P ≤ 0.05) in severe cases compared with non-severe cases. There was an increase in the serum level of IL-12 in severe cases, which was 33.340 ng/L, and in non-severe cases, it was 20.913 ng/L (P ≤ 0.000). For ACE-2, this study revealed a significant difference in serum levels in severe cases (P ≤ 0.05) when compared with non-severe cases. The serum level of ACE-2 in severe cases was 11.023 ng/ml, and in non-severe cases, it was 5.443 ng/ml (P ≤ 0.000). The result for the IL-12A gene showed nine SNPs as follows: rs1460141649 (CG, GG, and CC), with the highest prevalence being CC (wild type) in severe COVID-19 patients at 84.7% and 92.5% respectively, statistically non-significant (P > 0.05). rs903858723 (TT, TG, TC, CC, GG, and GC) had the highest prevalence of wild type in severe patients at 78.3% and 85.2% respectively, statistically non-significant (P > 0.05). rs772904833 (AA, AG, GG) had the wild type highest in severe patients at 78.3% and 83.4%, non-significant (P > 0.05). rs1208781994 (GG, GC, CC) had wild type prevalence at 78.3% and 87%, non-significant (P > 0.05). rs1720482004 (AA, AG, AC) had wild type prevalence at 100% and 89.6%, non-significant (P > 0.05). rs550206516 (GG, GA, AA) had 100% wild type prevalence in severe patients, non-significant (P > 0.05). The SNP rs4986960 on IL-12A showed a significant difference between GG and GT genotypes (P = 0.04), meaning that this SNP contributed to infection and severity in COVID-19. For the IL-12B gene, a novel SNP at position 159315957 showed a significant difference between AA and AG genotypes (P = 0.01), indicating that this SNP contributed to infection and severity. The ACE-2-2 gene revealed thirteen SNPs (GRCh38.p13) as follows: rs775089013, rs1180242786, rs760347219, rs768110251, rs776135947, rs761675562, rs199651576, rs1308021517, rs1463669655, rs746202722, rs201035388, and rs779538833. There was no significant difference between these SNPs and COVID-19 severity because all patients had the wild genotype, and heterozygous and homozygous genotypes were absent, except for rs1482922566 and rs1463669655, where all patients had the heterozygous genotype and wild type and homozygous were absent. From these findings, this study concluded that both ACE-2 and IL-12 contributed to the severity of infection in COVID-19 patients in the immunological study, but for the genetic study, polymorphisms in the ACE-2-2 gene were not associated with severity, whereas polymorphisms in IL-12A and IL-12B were associated with the severity of COVID-19 patients.