Comparison of the efficacy of combined budesonide and fexofenadine versus combined fluticasone propionate and fexofenadine on the expression of class-4 semaphorins and their receptors in the peripheral blood cells of patients with allergic rhinitis.

Background: Allergic rhinitis (AR) is a common immunoglobulin (Ig) E-mediated disease. This study aimed to evaluate the gene expression levels of class 4 semaphorins and their receptors in AR patients before and after treatment with budesonide and fexofenadine (B/F) compared to fluticasone propionate and fexofenadine (FP/F). Methods: In this study, 29 AR patients (age 34.4 ± 1.2 years, 18 men and 11 women) were treated with B/F, and 24 AR patients (age 32.8 ± 1.9 years, 15 men and 9 women) were treated with FP/F for one month. Before and after treatment, peripheral blood samples were taken from patients. The expression levels of SEMA4A, SEMA4C, SEMA4D, Plexin-B2, and Plexin-D1 genes were measured using the qPCR method. In addition, the serum levels of IgE were measured using an enzyme-linked immunosorbent assay (ELISA). Results: The expression levels of SEMA4A (P = 0.011), 4C (P = 0.017), Plexin-B2 (P = 0.0005), and Plexin-D1 (P = 0.008) remarkably increased in AR patients treated with B/F. Our results show a significant reduction in the gene expression levels of SEMA4A (P = 0.002), 4C (P = 0.014), 4D (P = 0.003), Plexin-B2 (P = 0.033), and Plexin-D1 (P = 0.035) after treatment with FP/F. The serum levels of IgE increased in FP/F treated group (P = 0.017) and conversely decreased in the treated group with B/F (P = 0.019). Moreover, the percentages of eosinophils were reduced in both FP/F and B/F groups (P = 0.015 and P = 0.0001, respectively). Conclusion: In conclusion, concomitant use of fexofenadine and fluticasone propionate reduced SEMA4A, 4C, 4D, Plexin-B2, and Plexin-D1, while the SEMA4A, 4C, Plexin-B2, and Plexin-D1 gene expression levels were increased in the patient group treated with B/F.

Association of Single Nucleotide Polymorphisms (SNPs) of Chemoattractant Receptor23 (ChemR23) Gene with Susceptibility to Allergic Rhinitis.

The chemoattractant Receptor23 (ChemR23) plays an essential role in triggering and resolving acute inflammation. This study aimed to evaluate the association between four potentially functional SNPs of the chemR23 gene (rs4373981 G > C, rs73201532 C > T, rs35121177 G > A, and rs4964676 G > A) with susceptibility to Allergic rhinitis (AR). 130 patients with allergic rhinitis and 130 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings showed that genotypes and alleles frequencies were not significantly different between patient and control groups (p > 0.05). Furthermore, haplotype analysis (rs4373981, rs73201532, and rs4964676, respectively) revealed a protective effect of CTG, GTA, and GTG haplotypes against AR (p = 0.009, p = 0.0001, p = 0.001, respectively), and CCG, GCA, and GCG haplotypes of ChemR23 polymorphisms were associated with increased risk of AR (p = 0.03, p = 0.02, p = 0.0002, respectively). These findings suggested a possible role for ChemR23 in the pathogenesis of AR.

Association of IFIH1 and DDX58 genes polymorphism with susceptibility to COVID-19.

Pattern recognition receptors of the innate immune system, such as RIG-I and MDA5, are responsible for recognizing viruses and inducing interferon production. Genetic polymorphisms in the coding regions of RLR may be associated with the severity of COVID-19. Considering the contribution of the RLR signaling in immune-mediated reactions, this study investigated the association between three SNP in the coding region of IFIH1 and DDX58 genes with the susceptibility to COVID-19 in the Kermanshah population, Iran. 177 patients with severe and 182 with mild COVID-19 were admitted for this study. Genomic DNA was extracted from peripheral blood leukocytes of patients to determine the genotypes of two SNPs, rs1990760(C>T) and rs3747517(T>C) IFIH1 gene and rs10813831(G>A) DDX58 gene using PCR-RFLP method. Our results showed that the frequency of the AA genotype of rs10813831(G>A) was associated with susceptibility to COVID-19 compared to the GG genotype (p = 0.017, OR = 2.593, 95% CI 1.173-5.736). We also observed a statistically significant difference in the recessive model for SNPs rs10813831 variant (AA versus GG + GA, p = 0.003, OR = 2.901, 95% CI 1.405-6.103). Furthermore, No significant association was found between rs1990760 (C>T) and rs3747517(T>C) of IFIH1 gene polymorphisms with COVID-19. Our findings suggest that DDX58 rs10813831(A>G) polymorphism may be associated with COVID-19 severity in the Kermanshah population, Iran.

Association of ANRIL Gene Single-Nucleotide Polymorphisms With Allergic Rhinitis in Kurdish Population From Kermanshah, Iran.

Background: Allergic rhinitis (AR) is the most common inflammatory disorder of the upper airway caused by aberrant immune responses to allergens in genetically predisposed individuals. Recently, the long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) has been identified as a novel genetic factor associated with increased AR risk. Objectives: This study aimed to evaluate the potential correlation of ANRIL gene single nucleotide polymorphisms (SNPs) with AR risk in the Kurdish population of Kermanshah, Iran. Methods: In this case-control study, 130 AR patients and 130 healthy controls were recruited to genotype for two SNPs of the ANRIL gene (rs1333048 and rs10757278) using the Tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Results: Our results showed no significant difference for the alleles and genotypes frequency distribution of lncRNA ANRIL SNPs (rs1333048 and rs10757278) between AR patients and healthy controls (p > 0.05). Additionally, the dominant, additive and recessive genetic models of both SNPs were not associated with altered susceptibility to AR risk (p > 0.05). Conclusion: The results demonstrated that the ANRIL gene rs1333048 and rs10757278 polymorphisms might not be associated with susceptibility to AR in the Kurdish population of Kermanshah, Iran.

Co-treatment with Fexofenadine and Budesonide Increases FoxP3 Gene Expression in Patients with Allergic Rhinitis.

BACKGROUND: T helper type 2 (Th2), Th17, and regulatory T cells (Tregs) play essential roles in the pathogenesis and control of allergic rhinitis (AR). Fexofenadine and budesonide are first-line treatments for AR. This study aimed to investigate the effect of co-treatment with fexofenadine and budesonide on the expression of Th2, Th17, and Treg-specific transcription factors (GATA-binding protein 3 [GATA-3], RAR-related orphan receptor gamma [RORγt], and forkhead box P3 [FoxP3], respectively) in AR patients. METHODS: In this study, 29 AR patients were co-treated with fexofenadine and budesonide for 1 month. Blood was collected from AR patients before and after 1 month of treatment. The gene expression levels of GATA-3, RORγt, and FoxP3 transcription factors in blood samples were measured. In addition, serum immunoglobulin E (IgE) levels and eosinophil percentages in blood samples were determined. FINDINGS: The expression level of FoxP3 increased significantly after treatment compared with that before treatment (P < .001). In contrast, GATA-3 and RORγt expression levels did not show any noticeable changes. In addition, the percentage of peripheral blood eosinophils significantly decreased (P < .01). Serum IgE levels decreased compared with those before treatment, but the difference was not statistically significant. Furthermore, the clinical symptoms of the patients improved compared with those before treatment. CONCLUSION: Our results showed that combined treatment with fexofenadine and budesonide increased the expression level of the FoxP3 gene, decreased the percentage of peripheral blood eosinophils, and improved the clinical symptoms of AR patients. This regimen appears to improve disease symptoms, at least in part by increasing the Treg population and decreasing the eosinophil population.

Association of Rs7217186 Polymorphism of Arachidonic Acid 15-Lipoxygenase (ALOX15) Gene with Susceptibility to Allergic Rhinitis.

Background: Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa, caused by exposure to environmental allergens. It is known that 15-lipoxygenase (15-LOX) is involved in the biosynthetic pathways of anti-inflammatory lipid mediators, including resolvins and protectins. Methods: In this study, which was performed on 130 AR patients and 130 healthy controls, we aimed to investigate the association of susceptibility to AR with two selected single-nucleotide polymorphisms (SNPs), that is, rs2619112:A>G and rs7217186:C>T, in the intron regions of arachidonic acid 15-LOX (ALOX15) gene, using SNPinfo and Regulome DB tools. Results: The results showed that the CT genotype of rs7217186: C>T was significantly associated with the increased risk of AR compared to the CC genotype (P= 0.037, OR=1.943, CI: 1.038-0.638). However, there was no strong evidence of the association of rs2619112: A>G with susceptibility to AR (P> 0.05). Conclusions: The present results indicated that rs7217186 polymorphism of ALOX15 gene might be a potential biomarker for susceptibility to AR.

Evaluation of the relationship between IL-6 gene single nucleotide polymorphisms and the severity of COVID-19 in an Iranian population.

BACKGROUND: Emerged coronavirus disease 2019 (COVID-19) is a pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Disease severity is associated with elevated levels of proinflammatory cytokines, such as interleukin-6 (IL-6). Genetic polymorphisms in the regulatory regions of cytokine genes may be associated with differential cytokine production in COVID-19 patients. This study aimed to investigate the association between three potentially functional single-nucleotide polymorphisms (SNPs) in the promoter region of IL-6 and the severity of susceptibility to COVID-19 in an Iranian population. METHODS: In total, 346 individuals (175 patients with severe COVID-19 and 171 patients with mild COVID-19) were recruited for this cohort study. Genomic DNA was extracted from peripheral blood leukocytes of patients to determine the genotypes of three selected SNPs (rs1800795 (-174 G > C), rs1800796 (-572 G > C), and rs1800797 (-597 G > A)) in the promoter region of the IL-6 gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: There were no significant differences in the genotype or allele distribution of selected SNPs (rs1800795 (-174 G > C), rs1800796 (-572 G > C), and rs1800797 (-597 G > A)) in the promoter region of the IL-6 gene in patients with severe COVID-19 and patients with mild COVID-19. DISCUSSION: Our study indicated that these SNPs are not associated with COVID-19 severity in the Kurdish population from Kermanshah, Iran.

Association between IL-33 Gene Polymorphism (Rs7044343) and Risk of Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a T helper type 2 (Th2)-mediated upper airways disease in which genetics factors including cytokine genes play a prominent role. Interleukin-33 (IL-33) is a major cytokine for naive T cells polarization into Th2 phenotype as well as enhances the secretion of Th2 cytokines. The aim of the present study was to investigate the relationship between IL-33 single nucleotide polymorphisms (SNPs) and IL-33 serum level with Allergic rhinitis. METHODS: Blood samples were collected from 130 AR patients and 130 healthy individuals. SNPs (rs7044343 C > T, rs1929992 A > G, rs12551256 A > G) of IL-33 gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum level of IL-33 was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Statistical analysis showed that the TT genotype (OR = 1.996, CI: 1.168-3.412, P = .01), as well as the T allele (OR = 0.675, CI: 0.476-0.957, P = .02) of rs7044343 C > T were significantly associated with reduced risk of AR. In addition, individuals carrying the TT genotype were associated with lower levels of IL-33 compared to subjects with CC and CT genotypes; however, these differences were not statistically significant. No association was found between rs1929992 and rs12551256 variants and risk of AR, but the GG genotype from rs1929992 A > G was associated with increased serum levels of IL-33 in control group (p = .01). Furthermore, serum IL-33 levels were not significantly different between AR patients and healthy controls (p > .05). CONCLUSION: Our results suggest that the TT genotype of rs7044343 C > T may act as a protective agent against allergic rhinitis.

A comprehensive in Silico analysis of the functional and structural impact of single nucleotide polymorphisms (SNPs) in the human IL-33 gene.

Interleukin 33 (IL-33) is the latest member of the IL-1 cytokine family, which plays both pro - and anti-inflammatory functions. Numerous Single-nucleotide polymorphisms (SNPs) in the IL-33 gene have been recognized to be associated with a vast variety of inflammatory disorders. SNPs associated studies have become a crucial approach in uncovering the genetic background of human diseases. However, distinguishing the functional SNPs in a disease-related gene from a pool of both functional and neutral SNPs is a major challenge and needs multiple experiments of hundreds or thousands of SNPs in candidate genes. This study aimed to identify the possible deleterious SNPs in the IL-33 gene using bioinformatics predictive tools. The nonsynonymous SNPs (nsSNPs) were analyzed by SIFT, PolyPhen, PROVEAN, SNP&GO, MutPred, SNAP, PhD SNP, and I-Mutant tools. The Non-coding SNPs (ncSNPs) were also analyzed by SNPinfo and RegulomeDB tools. In conclusion, our in-silico analysis predicted 5 nsSNPs and 22 ncSNPs as potential candidates in the IL-33 gene for future genetic association studies.

Association of interleukin-12B rs6887695 with susceptibility to allergic rhinitis.

Interleukin-12 (IL-12) is a heterodimeric cytokine encoded by two separate genes, IL12A and IL12B, which may play a regulatory role in allergen-induced inflammation through CD4+ T-cell subsets polarization. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) in the IL12B gene with susceptibility to allergic rhinitis (AR). We performed a case-control study including 130 AR patients and 130 healthy controls to evaluate the possible association between IL12B gene SNPs (rs3212227, rs6887695) and the risk of AR using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our results showed no significant association between IL12B rs3212227 A > C polymorphism with AR. In contrast, the GC genotype of rs6887695 G > C was associated with susceptibility to AR in comparison with the GG genotype (p = 0.049, OR = 1.684, 95% CI: 1.002-2.83). We also observed a statistically significant difference in the additive model (GC versus GG + CC, p = 0.03, OR = 1.705, 95% CI: 1.040-2.794) for SNPs rs6887695. Furthermore, haplotypes analysis demonstrated that C-C haplotype was associated with an increased risk of AR (p = 0.01, OR = 1.845, 95% CI: 1.114-3.057). Our findings suggest that IL12B rs6887695 polymorphism may be a potential biomarker for susceptibility to AR in an Iranian population.