Background The COVID-19 pandemic remains an emerging public health crisis with serious adverse effects. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV--2) infection, targeting angiotensin-converting enzyme-2 (ACE2) receptor for cell entry. However, changes in the renin-angiotensin system (RAS) balance alter an individual’s susceptibility to COVID-19 infection. We aimed to evaluate the association between AGT rs699 C > T, ACE rs4646994 I/D, and AGTR1 rs5186 C > A variants and the risk of COVID-19 infection and the severity in a sample of the southeast Iranian population. Methods A total of 504 subjects, including 258 COVID-19 positives, and 246 healthy controls, were recruited. Genotyping of the ACE gene rs4646994, and AGT rs699, and AGTR1 rs5186 polymorphisms was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. Results Our results showed that the II genotype of ACE rs4646994 and the I allele decreased the risk of COVID-19 infection. Moreover, we found that the TC genotype and C allele of AGT rs699 increased the risk of COVID-19 infection. The AGTR1 rs5186 was not associated with COVID-19 infection. Also, we did not find any association between these polymorphisms and the severity of the disease. However, we found a significantly higher age and prevalence of diabetes and hypertension in patients with severe disease than a non-severe disease. Conclusions These findings suggest that ACE rs4646994 and AGT rs699 polymorphisms increase the risk of COVID-19 infection in a southeast Iranian population.

ABSTRACT. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, which encodes an intracellular lymphoid-specific phosphatase, is considered an important regulator of T-cell activation. We investigated a possible association between the PTPN22 C1858T (R620W) polymorphism and pulmonary tuberculosis in an Iranian population. Single nucleotide polymorphisms of PTPN22 C1858T (rs2476601) were genotyped in 172 pulmonary tuberculosis cases and 204 normal subjects from Zaheden, Iran. Frequencies of genotypes CC, CT and TT of the PTPN22 C1858T polymorphism were 98.3, 1.7 and 0% in the pulmonary tuberculosis patients, and 96.1, 3.9 and 0% in the control group, respectively (P = 0.239). The frequency of the minor (T) allele was 0.8% in pulmonary tuberculosis patients and 2.0% in controls. Significant differences were not observed in genotype or allele frequencies of PTPN22 C1858T in the comparison between pulmonary tuberculosis patients and healthy subjects in our Iranian population sample.

ABSTRACT. Susceptibility to tuberculosis may be influenced by variations in human genes. The P2X7 receptor is an ATP-gated cation channel expressed in immune cells, and it influences the release of proinflammatory cytokines from monocytes and macrophages. In the present study, we aimed to evaluate the impact of P2X7 gene rs2393799 (-762T/C) and rs1718119 (Thr348Ala) polymorphisms on patient susceptibility to pulmonary tuberculosis (PTB) in a sample of the Iranian population. This case-control study was performed using 150 PTB cases and 150 controls. P2X7 receptor polymorphisms were determined using tetra-amplification refractory mutation system-polymerase chain reaction. Genotype and allelic frequencies of the rs2393799 variant P2X7 gene polymorphisms in pulmonary tuberculosis within the P2X7 gene were significantly higher in the PTB patients than in the healthy controls. The genotypes were CC in 71, CT in 54, and TT in 25 PTB patients. The genotypes were CC in 104, CT in 40, and TT in 6 healthy controls. The results indicate a significant association between rs2393799 polymorphism of the P2X7 gene and susceptibility to PTB (CT vs CC: OR = 6.5, 95%CI = 2.5-16.9, P < 0.0001; TT vs CC: OR = 3.3, 95%CI = 1.2-8.9, P = 0.018; TC+TT vs CC: OR = 2.56, 95%CI = 1.59-4.12, P < 0.0001). The rs2393799 T allele is a risk factor for predisposition to PTB (OR = 2.53, 95%CI = 1.73-3.71, P < 0.0001). No association between the rs1718119 polymorphism and PTB was found. In conclusion, the rs2393799 polymorphism in the P2X7 gene may contribute to patient susceptibility to PTB in our study population.

Cysteine-cysteine chemokine ligand 5 (CCL5) with immunoregulatory and inflammatory activities has an important role in granuloma formations that activates and stimulates T-cells and macrophages. Cysteine-cysteine chemokine receptor 5 (CCR5) is a chemokine receptor, which is important for migration of immune cells to site of infection. In the present study we investigated the possible association between CCL5 -403G/A (rs2107538), CCL5 -28C/G (rs2280788) and CCR5 Δ32 polymorphisms and pulmonary tuberculosis (PTB) in an Iranian population. This case-control study was performed on 160 patients with pulmonary tuberculosis and 160 unrelated healthy subjects. The CCL5 -403G/A, CCL5 -28C/G and CCR5 Δ32 polymorphisms were genotyped by allele-specific polymerase chain reaction (AS-PCR), tetra amplification refractory mutation system polymerase chain reaction (T-ARMS PCR) and PCR, respectively. Our results showed that GA as well as GA+AA genotypes of CCL5 -403G/A (rs2107538) increased the risk of PTB in comparison with GG genotype (OR=1.70, 95% CI=1.03-2.81, P=0.038 and OR=1.64, 95% CI=1.00-2.68, P=0.049, respectively). No significant association was found between CCL5 -28C/G as well as CCR5 Δ32 polymorphism and PTB risk. In conclusion, our findings proposed that CCL5 -403G>A polymorphism may be a risk factor for susceptibility to PTB in our population. Larger sample sizes with different ethnicities are required to validate our findings.

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