Coronavirus disease 2019 (COVID-19) is a severe disease caused by a new variant of beta-coronavirus that first appeared in China. Human genetic factors, including polymorphisms, serve pivotal roles in the high transmission of SARS-CoV-2 and the stubbornly progressing sickness seen in a small but significant percentage of infected people; however, but these factors remain ill-defined. A total of 288 COVID-19 patients and 288 controls were genotyped for TMPRSS2 polymorphisms using both restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and amplification refractory mutation system (ARMS)-PCR techniques. Different genotypes of TMPRSS2 polymorphisms were compared in terms of disease susceptibility and mortality. The statistical analysis showed that minor alleles of all studied variants statistically increased the risk of COVID-19, except for the rs75603675 C > A variant. The T allele of rs12329760 conferred an increased risk of COVID-19. Moreover, the AG/AC/TT/AG combination of genotypes significantly enhanced the risk of COVID-19 in our population. Different haplotypes of rs17854725/rs75603675/rs12329760/rs4303795 polymorphisms, including GACA, GACG, GATG, GATA, AATA, ACCG, ACTG, ACTA, GCCA, and GCTG, were found to be associated with increased risk of the disease (odds ratio > 1). Regarding the clinical and paraclinical characteristics, a statistically significant difference was found between non-severe and severe forms except for gender, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and underlying diseases. In addition, case genotypes of TMPRSS2 rs17854725 A > G, rs12329760 C > T, and rs4303795 A > G were significantly different regarding severe and non-severe forms of the disease ( P -value < 0.001). Specifically, death was more frequent in carriers of the AG genotype of rs17854725 A > G ( P -value = 0.022). Patients who carry the minor alleles of the four studied TMPRSS2 variants were rather vulnerable to COVID-19 infection. Our findings indicated that rs17854725 A > G (AA vs. AG and AA vs. GG), rs12329760 C > T (CC vs. CT and CC vs. TT), and rs4303795 A > G (AA vs. AG) genotypes of TMPRSS2 variations are associated with a more invasive disorder pattern. More studies on larger populations are needed to confirm our results. Supplementary Information The online version contains supplementary material available at 10.1007/s12010-022-03885-w.

The present coronavirus disease 2019 is spreading rapidly and existing data has suggested a number of susceptibility factors for developing a severe course of the disease. The current case-control experiment is aimed to study the associations of genetic polymorphisms in tumor necrosis factors (TNFs) with COVID-19 and its mortality rate. A total of 550 participants (275 subjects and 275 controls) were enrolled. The tetra-amplification refractory mutation system polymerase chain reaction technique was recruited to detect −308G>A TNFα and +252A>G TNFβ polymorphisms among the Iranian subjects. We demonstrated that carriers of the G allele of TNFβ-252A/G, rs909253 A>G were more frequent in COVID-19 subjects compared to the healthy group and this allele statistically increased the disease risk (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.23-1.96, p < 0.0001). At the same time, the A allele of TNFα-311A/G, rs1800629 G>A moderately decreased the risk of COVID-19 (OR = 0.68, 95% CI = 0.53-0.86, p < 0.002). Also, we analyzed the various genotypes regarding the para-clinical and disorder severity; we found that in the AA genotype of TNFβ-252A/G (rs909253 A>G), the computed tomography scan pattern was different in comparison to cases carrying the AG genotype with p 1 < 0.001. In addition, in the severe cases of COVID-19, leukocyte and neutrophil count and duration of intensive care unit hospitalization in the deceased patients were significantly increased (p < 0.001). Moreover, the TNFα-311A/G (rs1800629 G>A) variant is likely to change the pattern of splicing factor sites. Our findings provided deep insights into the relationship between TNFα/TNFβ polymorphisms and severe acute respiratory syndrome coronavirus 2. Replicated studies may give scientific evidence for exploring molecular mechanisms of COVID-19 in other ethnicities.

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Type 2 diabetes mellitus (T2DM) is a complex heterogeneous disease resulting from the environment and genetic interactions. Lately, genetic association studies have shown that polymorphisms in long noncoding RNAs (lncRNAs) are associated with T2DM susceptibility. This preliminary study is aimed at investigating if HOX transcript antisense RNA (HOTAIR) polymorphisms contribute to T2DM development. Five hundred clinically diagnosed T2DM cases and 500 healthy controls were recruited from the southeast Iranian population. Genomic DNA was isolated from nucleated blood cells and genotyped for MspI (C/T) (rs920778) and AluI (A/G) (rs4759314) polymorphisms using the PCR-RFLP technique. For genotyping rs12826786 C/T and rs1899663 G/T variants, ARMS-PCR method was applied. Our findings indicated that HOTAIR rs920778 C/T, rs12826786 C/T, and rs4759314 A/G polymorphisms have a significant positive association with T2DM, while a negative association was observed between rs1899663 G/T T2DM susceptibility. Significant associations were also observed between rs920778 C/T and HDL-C as well as s4759314 A/G and both FBS and LDL-C in T2DM patients. Haplotype analysis indicated that the CGCG, CTTG, TGTA, and TTTG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 significantly enhanced T2DM risk by 1.47, 1.96, 2.81, and 4.80 folds, respectively. No strong linkage disequilibrium was found between the four HOTAIR SNPs. We firstly reported that HOTAIR rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphisms might influence T2DM susceptibility by modulating different signaling pathways and could be regarded as potential prognostic markers in T2DM patients.

Cytokines play pivotal functions in coronavirus disease 2019 pathogenesis. However, little is known about the rationale and importance of genetic variations associated with immune system responses, so-called "immunogenetic profiling." We studied whether polymorphisms of IL6, IL6R, TNFA, and IL1RN affect the disorder severity and outcome in patients infected with COVID19. We recruited 317 hospitalized patients with laboratory-confirmed COVID-19 from Bu-Ali hospital and 317 high-risk participants who had high exposure to COVID-19 patients but with a negative real-time-polymerase chain reaction (PCR) test. Multiple regression analyses were applied. We indicated that participants carrying the A allele in TNFA-rs361525, G>A (p < .004), the C allele in IL1RN-rs419598 T>C (p < .004), the A allele in IL6R-rs2228145, A>C (p = .047) are more susceptible to develop COVID-19. In contrast, those who carry the G allele of IL6-rs2069827, G>T (p = .01), are more protected from COVID-19. Also, we compared the various genotypes regarding the disorder severity and poor prognosis; we found that the AA genotype in TNFA is related to more aggressive illness and bad prognostic in contrast to the other inflammatory cytokines' genotypes. In addition, a high level of inflammatory indications, such as neutrophil-to-lymphocyte ratio and systemic immuneinflammation index, was observed in deceased patients compared with the survived subjects (p < .0001). We advised considering inflammatory cytokines polymorphisms as the main item to realize the therapeutic response against the acute respiratory distress syndrome induced by the SARS-CoV-2 virus.