Interleukin-1 Gene Research Articles

Impact of the Functional VNTR Variants of the Interleukin-1 Receptor Antagonist and Interleukin-4 Genes on Oral Squamous Cell Carcinoma

Impact of the Functional VNTR Variants of the Interleukin-1 Receptor Antagonist and Interleukin-4 Genes on Oral Squamous Cell Carcinoma

Gene expression and antibody response in chicken against Salmonella Typhimurium challenge

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses to poultry industry. Furthermore, S. Typhimurium is also able to cause infection in humans, characterized by acute gastrointestinal disease. A study was conducted to investigate antibody response and expression kinetics of interferon gamma (IFNγ), interleukin (IL-12, and IL-18) genes in broiler chicken at 0, 1, 3, 5, 7, 9, 11, 13, and 15D post infection following experimental infection of S. Typhimurium. Immunological studies showed higher titres of IgG and IgM in the infected group as compared to the age-matched un-infected control group. The Real-Time PCR-based gene expression analysis revealed significant increase of IFNγ, IL-12, and IL-18 mRNA levels in the infected group as compared to their respective controls (P < 0.05). The present study shall help in understanding the immune responses in birds, thus allowing development of more effective vaccines and vaccination strategies.

The Effects of Selenium Supplementation on Clinical Symptoms and Gene Expression Related to Inflammation and Vascular Endothelial Growth Factor in Infertile Women Candidate for In Vitro Fertilization.

This study was performed to determine the effects of selenium supplementation on clinical symptoms and gene expression related to inflammatory markers in infertile women with polycystic ovary syndrome (PCOS) who were candidate for in vitro fertilization (IVF). Thirty-six women candidate for IVF were recruited in this randomized double-blinded, placebo-controlled trial. They (n = 18/group) were randomly assigned into intervention groups to take either 200μg/day of selenium or placebo for 8weeks. RT-PCR findings indicated that selenium supplementation downregulated gene expression of interleukin-1 (IL-1) (P < 0.004) and tumor necrosis factor alpha (TNF-α) (P = 0.02) in lymphocytes of patients with PCOS compared with the placebo. In addition, selenium supplementation upregulated gene expression of vascular endothelial growth factor (VEGF) (P = 0.001) in lymphocytes of patients with PCOS compared with the placebo. Selenium supplementation had no significant effect on clinical symptoms and gene expression of IL-8 (P = 0.10) and transforming growth factor beta (TGF-β) (P = 0.63). Overall, our findings documented that selenium supplementation for 8weeks to infertile women candidate for IVF improved IL-1, TNF-α, and VEGF gene expression, though selenium had no effect on clinical symptoms and, IL-8 and TGF-β gene expression. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N23.

Sequence characterization and expression pattern analysis of six kinds of IL-17 family genes in the Asian swamp eel (Monopterus albus)

Interleukin-17 (IL-17) is an important cytokine that plays a critical role in the inflammatory response and host defense against extracellular pathogens. In the present study, six novel IL-17 family genes (MaIL-17) were identified by analyzing Asian swamp eel (Monopterus albus) genome. Sequence analysis revealed that the MaIL-17 family genes shared similar features, comprising a signal peptide, an IL-17 superfamily region, and four conserved cysteines. Phylogenetic analysis showed that the MaIL-17 genes were clustered together with their corresponding IL-17 genes from other species. The similarity and identity of all IL-17 family genes indicated that the MaIL-17 genes are conserved among teleosts, while Ma-IL-17D is more conserved than the other Ma-IL-17s. Except for MaIL-17A/F3 and MaIL-17D, all MaIL-17s shared the same genomic structure as the genes from other fish, namely three exons and two introns. The MaIL-17s showed conserved synteny among fish, and we found that the MaIL-17D locus has a more conserved syntenic relationship with the loci from other fish and humans. These results demonstrated that MaIL-17D and human IL-17D might have evolved from a common ancestral gene and subsequently diverged. The analysis of swamp eel reference genes revealed that EEF1A1 (encoding eukaryotic translation elongation factor 1 alpha 1) was an ideal reference gene for accurate real-time qRT-PCR normalization in the swamp eel. The MaIL-17 genes are widely distributed throughout tissues, suggesting that MaIL-17s carry out their biological functions in immune and non-immune tissues compartments. The transcript of Ma-IL17s exhibited different fold changes in head kidney cells in response to Aeromonas veronii phorbol 12-myristate 13-acetate (PMA) and polyinosinic:polycytidylic acid (poly I:C) challenge, showing that MaIL-17A/F1 has stronger antiviral activities compared with other MaIL-17 family genes, and that MaIL-17A/F3 and MaIL-17A/F2 possess stronger effects against extracellular pathogens compared with the others; however, MaIL-17C2 and MaIL-17D may play vital roles during pathogen infection. The differential immune responses of these genes to Aeromonas veronii, PMA and poly I:C implied distinct mechanisms of host defense against extracellular pathogens.

Interleukin gene polymorphisms in chronic periodontitis: A case-control study in the Indian population

ObjectiveThe aim of the present study was to investigate the possible association between seven Interleukin (IL) gene polymorphisms and their interaction with the chronic inflammatory oral disease, chronic periodontitis in Indian population. DesignA total of 357 study subjects (157 with chronic periodontitis and 200 with healthy control) were genotyped for IL1A -889C/T (rs1800587), IL1B -31C/T (rs1143627), IL1B -511A/G (rs16944), IL1B + 3954C/T (rs1143634), IL2 −330 T/G (rs2069762), IL4 -33C/T (rs2070874), IL6 −597 G/A (rs1800797), IL8 -251A/T (rs4073), IL10 -819C/T (rs1800871), IL10 -592A/C (rs1800872) and IL13 -1111C/T (rs1800925). Statistical analysis was performed using the statistical software package SPSS v16. SNPassoc and Multifactor Dimensionality Reduction algorithm v3.0.2. ResultsWe found that the statistically significant association of IL1A-889C/T (rs1800587), IL1B -31C/T (rs1143627), IL1B -511A/G (rs16944) and IL1B + 3954C/T (rs1143634) gene polymorphisms with increased susceptibility of chronic periodontitis. The best gene-gene interaction model was IL1B(-31C/T) X IL1B(+3954C/T) X IL10(-819C/T) with 10/10 cross validation consistency. The variant allele of IL1A, IL1B, IL10 and IL13 were seemed to be linked with chronic periodontitis increased susceptibility. The results of this study also indicate that epidemiological factors especially oral habits also play an important role in the development of chronic periodontitis. ConclusionsThis study concludes IL1A -889C/T (rs1800587), IL1B -31C/T (rs1143627), IL1B -511A/G (rs16944), IL1B + 3954C/T (rs1143634), IL10 -819C/T (rs1800871), IL10 -592A/C (rs1800872) and IL13 -1111C/T (rs1800925) gene polymorphisms are significantly associated with chronic periodontitis. This work also infers that the best interactive model comprised of IL1B and IL10 polymorphisms cumulatively increase the risk of chronic periodontitis.

Elucidation of the molecular mechanism underlying the anti-inflammatory activity of an effective and safe bipyrazole-based compound.

Since the synthesis of acetylsalicylic acid by Hoffmann in 1897, new classes of NSAIDs have been introduced; however, their side effects have limited their clinical applications. Consequently, our team has recently synthesized a novel bipyrazole compound that showed a satisfactory efficacy and safety profile. The aim of the current study was to elucidate the molecular mechanism of this bipyrazole compound. The anti-inflammatory efficacy of the compound was assessed using formalin-induced paw edema test. Computer-assisted simulation docking experiments were carried out. Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), tumor necrosis factor-alpha (TNFα), interleukin-1 (IL1) and interleukin-10 (IL10) gene expression were quantified with real-time polymerase chain reaction (RT-PCR) using SYBR Green technology. The samples were taken from the plantar paw of mice after formalin local injection. The efficacy of the bipyrazole compound was similar to that of indomethacin, diclofenac, and celecoxib, as proven by the formalin-induced paw edema. Docking study indicated a superior binding score for the studied compound relative to celecoxib, indomethacin, and diclofenac. RT-PCR assessment revealed a significant decrease in iNOS, COX-2, and TNFα gene expression in the bipyrazole-treated group. Moreover, a reduction in IL1 and nNOS gene expression levels and an increase in IL10 level were detected despite being insignificant compared to the control group. These findings revealed the superiority of the newly synthesized bipyrazole compound not only on the binding site, but also by inhibiting most of the inflammatory mediators including TNF-α.

HIV Replication in Humanized IL-3/GM-CSF-Transgenic NOG Mice.

The development of mouse models that mimic the kinetics of Human Immunodeficiency Virus (HIV) infection is critical for the understanding of the pathogenesis of disease and for the design of novel therapeutic strategies. Here, we describe the dynamics of HIV infection in humanized NOD/Shi-scid-IL2rγnull (NOG) mice bearing the human genes for interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (NOG-EXL mice). The kinetics of viral load, as well as the frequencies of T-cells, B-cells, Natural killer cells (NK), monocytes, and dendritic cells in blood and secondary lymphoid organs were evaluated throughout the time of infection. In comparison with a non-transgenic humanized mouse (NSG) strain, lymphoid and myeloid populations were more efficiently engrafted in humanized NOG-EXL mice, both in peripheral blood and lymphoid tissues. In addition, HIV actively replicated in humanized NOG-EXL mice, and infection induced a decrease in the percentage of CD4+ T-cells, inversion of the CD4:CD8 ratio, and changes in some cell populations, such as monocytes and dendritic cells, that recapitulated those found in human natural infection. Thus, the humanized IL-3/GM-CSF-transgenic NOG mouse model is suitable for the study of the dynamics of HIV infection and provides a tool for basic and preclinical studies.

ANTI-INFLAMMATORY AND ANTIOXIDANT EFFECTS OF POMEGRANATE ON ACETIC ACID-INDUCED ULCERATIVE COLITIS IN RATS

The present study was designed to investigate the protective effect of pomegranate extract on some blood and antioxidant parameters in addition to interleukin-1 (IL-1) and inducible nitric oxide (iNOS) gene expression of colon tissue in acetic acid-induced ulcerative colitis in rats. Forty rats were divided into four equal groups. Group I (c) group (control normal group) received no drugs. Group II (AA) group (Acetic acid induced ulcerative colitis group) rats were administrated with 2 ml of acetic acid (AA) 4% intracolonic as a single dose. Group III (PGFE) group (Pomegranate group) rats were administrated with pomegranate orally (500 mg/kg, b.wt/day for 14 days. Group VI (PGFE+AA) group (PGFE protected plus AA 4% induced ulcerative colitis group) rats were administrated with PGFE orally (500 mg/kg, b.wt/day for 14 days and at the 11th day was administrated intracolonic as a single dose with 2 ml of AA 4%. The obtained results showed that a significant decrease in neutrophils to lymphocytes ratio (N/LR) and increase in lymphocytes to monocytes ratio (L/MR) in (PGFE+AA) group when compared with (AA) group. Meanwhile, malondialdehyde (MDA) and nitric oxide (NO) were significantly decreased with significant down-regulation in IL-1s and iNOS gene expression levels were obtained in colon tissue of (PGFE+AA) group when compared with (AA) group. The results revealed that pomegranate has protective, anti-inflammatory and antioxidant effects in experimental model of ulcerative colitis in induced rats.

Interleukin-3 Polymorphism is Associated with Miscarriage of Fresh in Vitro Fertilization Cycles.

The aim of this study was to examine the association between interleukin (IL) genes polymorphisms and in vitro fertilization (IVF) outcome. A prospective cohort analysis was performed at a Women’s Hospital IVF centre of 1015 female patients undergoing fresh non-donor IVF cycles. The effects of the following six single nucleotide polymorphisms (SNPs) in five IL genes on IVF outcomes were explored: IL-1α (rs1800587 C/T), IL-3 (rs40401 C/T), IL-6 (rs1800795 C/G), IL-15 (rs3806798 A/T), IL-18 (rs187238 C/G) and IL-18 (rs1946518 G/T). The main outcome measures included clinical pregnancy, embryo implantation, abortion and live birth rates. There were no statistically significant differences in clinical pregnancy, embryo implantation and live birth rates in the analysis of 1015 patients attempting their first cycle of IVF. Infertile women with IL-3 homozygous major genotype had a higher abortion rate than those with heterozygous and homozygous minor genotype (16.5% vs. 7.9%, P = 0.025). In conclusion, our results indicated that the IL-3 rs40401 polymorphism is associated with increased risk of abortion of IVF patients. Future studies with inclusion of other ethnic populations must be conducted to confirm the findings of this study.

Association between chronic obstructive pulmonary disease and interleukins gene variants: A systematic review and meta-analysis

Interleukins are cytokines involved in systemic inflammation and immune system regulation. Many studies have investigated the association between common genetic variations in interleukin-coding genes and COPD susceptibility. In this study, a systematic review and meta-analysis was performed to evaluate the association between interleukin gene variations and COPD pathogenesis.Association studies were retrieved from PubMed and Google Scholar databases using the standard systematic search strategy. A total of 26 different studies evaluating eight polymorphisms in four interleukin genes were included in this study.In overall comparisons, IL1β-rs16944, -rs1143627, -rs1143634, IL13-rs20541 polymorphisms were found not to be associated with the increased risk for developing COPD. However, IL1RN-rs2234663 and IL13-rs1800925 showed a strong association with COPD. We showed that the CC genotype carriers of the IL6-rs1800795 are at significantly higher risk of developing COPD (OR = 1.31, 95% CI: 1.04–1.64, P = 0.01) compared to GG carriers. In case of IL6-rs1800796, individuals with CC and CG genotypes showed a lower risk to develop COPD (OR = 0.46, 95%CI: 0.32–0.66, P > 0.00).This updated meta-analysis strongly supports the association of IL1RN-rs2234663, IL6-rs1800795, -rs1800795 and IL13-rs1800925 variants with COPD.

Evolution and function analysis of interleukin-17 gene from Pinctada fucata martensii

Interleukin-17 (IL-17) is a proinflammatory cytokine that plays an important role in immune responses. In this study, we identified 57 IL-17 genes from the genomes of six marine invertebrates, including Pinctada fucata martensii, Crassostrea gigas, Lottia gigantea, Capitella teleta, Mizuhopecten yessoensis, and Mytilus galloprovincialis. Phylogenetic analysis showed that all invertebrate IL-17 genes were clustered into one group, implying that invertebrate IL-17 evolved from one common ancestral gene. From the extron–intron analysis, we found many intronless IL-17 genes in mollusks, which may be caused by retroposition. Tissue and development transcriptomic analysis showed that the expression of PmIL-17 was tissue and developmental stage-specific. Moreover, we cloned the full length of the IL-17-2 gene from P. f. martensii (PmIL-17-2) and explored its function in the immune response. The full-length cDNA of PmIL-17-2 is 719 bp, containing an open reading frame of 564 bp, a 5′ -untranslated region (UTR) of 31 bp, and a 3′ -UTR of 124 bp with a 30 bp poly (A) tail. PmIL-17-2 had a strong response to lipopolysaccharide (LPS), indicating that the PmIL-17-2 participates in innate immune responses. In situ hybridization of hemocytes showed that PmIL-17-2 was mainly produced by granulosa cells, and the number of the stained granulosa increased after LPS stimulation. These results lay the foundation for the research of IL-17 family in marine invertebrates.

Interleukin-1 Gene Variability and Plasma Levels in Czech Patients with Chronic Periodontitis and Diabetes Mellitus.

Recent studies have suggested a bidirectional relationship between chronic periodontitis (CP) and diabetes mellitus (DM). Immunoregulatory factors such as cytokines play an important role in etiopathogenesis of both diseases. The aim of this study was to analyze variability in interleukin-1 (IL-1) gene cluster and IL-1β plasma levels in patients with CP, DM, and a combination of both diseases. A total of 1016 individuals participating in this case-control study—225 healthy controls, 264 patients with CP, 132 with type 1 diabetes (T1DM), and 395 patients with type 2 diabetes (T2DM)—were genotyped using methods based on polymerase chain reaction for IL-1 gene polymorphisms (IL-1A (−889C/T, rs1800587), IL-1B (+3953C/T, rs1143634), and IL-1RN (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2)). Levels of IL-1β were measured by Luminex methods in subgroups of controls, CP, T1DM + CP, and T2DM + CP subjects. Although no significant associations were found in the genotype and allele frequencies of IL-1A (−889C/T), significant differences in the allele frequencies of IL-1B (+3953C/T) were observed between controls and CP patients (P < 0.05). In T1DM patients, IL-1RN∗S “short” allele and IL-1RN 12 genotype were significantly less frequent than those in controls (P < 0.01). In haplotype analysis, TTL haplotype decreased the risk of CP development (P < 0.01), whereas CCS and CTL haplotypes (P < 0.01 and P < 0.05) were associated with T1DM. Although IL-1β levels were measured significantly higher in mononuclear cells after stimulation by mitogens, HSP70, or selected periodontal bacteria than in unstimulated cells, IL-1 genotypes did not correlate with circulating IL-1β levels. In the Czech population, significant associations between the IL-1B polymorphism with CP and the IL-1RN variant with T1DM were found. Haplotype analysis suggests that variability in IL-1 gene cluster may be one of the factors in the CP and T1DM pathogenesis, although single variants of these polymorphisms are not substantial for protein production.

Gene polymorphisms in the interleukins gene and the risk of acute pancreatitis: A meta-analysis

Single nucleotide polymorphisms (SNPs) within the interleukins (IL) gene may affect the risk of acute pancreatitis. Many epidemiological studies have reported an association between the IL gene and acute pancreatitis risk, but the results remain inconsistent. Given the controversial available data, we carried out a meta-analysis to systematically evaluate and clarify the association between IL gene polymorphisms and AP. A systematic search of studies for this association was obtained from the PubMed, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) databases until June 1, 2017. We also searched the references of the included studies to identify additional studies. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to pool the effect size. Stata12.0 was used for whole statistical analysis. Fifteen studies that contained 3371 AP cases and 3506 controls were included in final combination. Overall, a significant association was found between the IL-8-251 T/A (rs4073) polymorphism, the IL-10-1082 A/G (rs1800896) polymorphism and the AP risk in four genetic models (homozygote model, recessive model, dominant model, allele model). Meanwhile, individuals with IL-1β+3954 C/T (rs1143634, (homozygote model, recessive model)), IL-1β -511 C/T (rs16944, (dominant model)) and IL-6-634C/G (rs1800796, (allele model)) polymorphism were associated with an increased risk of AP. No evidence of an association was found between IL and 10-592 C/A (rs1800872) and IL-10-819 C/T (rs1800871) polymorphism and AP risk.

The significance of interleukin 4 (IL-4) (590-C/T) gene polymorphism in Iraqi patients with type 2 diabetes mellitus: A case-control study

One of well knows ant-inflammatory cytokines is Interleukin 4 (IL-4). It plays major roles in the control of immune responses at various levels. It is involved in the proliferation of activated B and T cells, inhibition of type 1 T helper differentiation, and promotion of type 2 T helper cell differentiation, control of B cell maturation (10-13). Moreover, it is involved in the growth, apoptosis, proliferation, and maturation of other hemopoietic and nonhemopoietic cells (14). Previous studies have investigated its role in allergic and autoimmune disorders (14-17). The gene for IL-4 is located at chromosome 5 within the long arm and possesses four exons (18). Several authors have shown a possible association of IL-4 gene polymorphism to a number of clinical disorders such as multiple sclerosis, atopic dermatitis, rheumatoid arthritis, and asthma (19-21). IL- 4 gene polymorphism has been linked to type 1 diabetes mellitus, but we in the current study aimed at investigating the significance of IL-4 590C/T (rs2243250) gene polymorphism in relation to type 2 diabetes and its long term complications. This study was aimed to assess the significance of IL-4 590C/T (rs2243250) gene polymorphism in relation to type 2 diabetes and its long term complications. The present case-control study was carried out at the diabetes center in Al-Diwaniayh Teaching Hospital, Al-Diwaniyah Province, Iraq. The study started in January 2019 and ended on July 2019. The study included 32 types 2 diabetes mellitus patients and 47 apparently healthy control subjects. Five ml sample of venous blood (antecubital vein) was obtained for the purpose of PCR analysis of IL-4 (590-C/T) gene polymorphism. The results of currents study revealed that the distribution of patients with type 2 diabetes was 21 (65.6 %), 9 (28.1 %) and 2 (6.3 %) as CC, CT, and TT genotypes; whereas, the distribution of control subjects was 33 (70.2 %), 10 (21.3 %) and 4 (8.4 %), as CC, CT, and TT genotypes. There was no significant difference in the frequency distribution of diabetic patients and control subjects according to IL- 4rs2243250 genotype (P = 0.757). IL- 4rs2243250 genotype polymorphism was not significantly correlated to retinopathy, nephropathy, neuropathy, CVA, IHD and dyslipidemia (P > 0.05), IL-4 IL- 4rs2243250 genotype polymorphism is neither associated with type 2 diabetes mellitus nor is linked to its long term microvascular and or macrovascular complications.

Regulatory effects of hemp seed/evening primrose oil supplement in comparison with rapamycin on the expression of the mammalian target of rapamycin-complex 2 and interleukin-10 genes in experimental autoimmune encephalomyelitis.

The mammalian target of rapamycin (mTOR) signaling plays a critical role in lipid synthesis and immune responses. The T regulatory cells (Treg) as suppressor of T cells, are a subset of T cells that modulate the immune system, maintain tolerance, and prevent autoimmune diseases.. The interleukin (IL) -10 derived from the Treg and T helper (Th) 2 is an anti-inflammatory cytokine in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Due to the exclusive roles of rapamycin (RAPA) in mTOR inhibition, we evaluated the regulatory effect of the hemp seed oil/evening primrose oil (HSO/EPO) supplement in comparison with RAPA in EAE. EAE was induced by using myelin oligodendrocyte glycoprotein peptide and complete freund’s adjuvant (CFA) in C57BL/6 mice, total mRNA was extracted from local lymph nodes and real-time polymerase chain reaction was used to evaluate the expression level of the rapamycin-insensitive companion of mTOR complex 2 (RICTOR) and IL-10 genes. The expression of IL-10 and RICTOR genes were significantly increased in HSO/EPO group. In contrast with RAPA groups, histological findings have shown that the HSO/EPO treated group remarkably reduced cell infiltration and promoted remyelination. The EPO/HSO has beneficial effects on the repair of myelin, which was confirmed by immunological and histological findings.

Association of IL-1 gene polymorphisms with chronic rhinosinusitis with and without nasal polyp.

BackgroundChronic rhinosinusitis (CRS) is one of the most common and complex chronic inflammatory disease of sinonasal mucosa. Even though the pathogenesis of CRS is multifactorial and still unclear, the role of cytokines especially interleukin-1 (IL-1) is being investigated worldwide in different population because of varying results obtained.ObjectiveTo study the association of IL-1 (A and B) gene polymorphisms with chronic rhinosinusitis with nasal polyp (CRSwNP) and without nasal polyp (CRSsNP), and other factors related.MethodsThis is a case-controlled study which include a total of 138 subjects recruited from Otorhinolaryngology-Head and Neck Surgery clinic in Hospital Universiti Sains Malaysia. Genotyping of the IL-1A (+4845G, +4845T) and IL-1B (−511C, −511T) were performed with restriction fragment length polymorphism analysis.ResultsThere was a statistical significant association between IL-1B (−511C, −511T) polymorphism with CRSwNP and CRSsNP (p < 0.001). The CT genotype of IL-1B was markedly increased in CRSwNP subjects (52.2%). However, there was no significant association found between IL-1A (+4845G, +4845T) with CRSwNP and CRSsNP (p = 0.093). No association was found in factors related to CRS, which included asthma, atopy, allergy, aspirin sensitivity, and family history of nasal polyp (p value of 0.382, 0.382, 0.144, >0.95, and 0.254, respectively).ConclusionThis study indicates an association of IL-1B (−511C, −511T) polymorphism with CRSwNP and CRSsNP in our population, hence there is a possibility of IL-1B involvement in modulating pathogenesis of CRS. There was no significant association of IL-1A (+4845G, +4845T) polymorphism with CRSwNP and CRSsNP, and other factors related.

The association between genetic polymorphisms of the interleukin-10, tumor necrosis factor-alpha, and annexin A5 gene loci and restenosis after percutaneous coronary angioplasty and stenting.

Background:Advances in the technology for percutaneous coronary angioplasty, such as coated stents, have reduced its complications, but restenosis remains an important clinical problem. The factors associated with an increased risk of restenosis include diabetes mellitus and multiple coronary artery disease. It is also possible that genetic factors play a role in restenosis although there are little data on this. We have investigated the association of three genetic markers of genes involved in inflammation leading to restenosis.Materials and Methods:In this case–control study, 306 unrelated Iranian patients who were thought to have restenosis on clinical grounds were investigated. Based on the results of angiography, 104 patients were found to have >50% stenosis within an implanted stent, and these were allocated to the in-stent restenosis (ISR) group; 202 patients with no in-stent stenosis or stenosis ≤50% were allocated to the non-ISR (NISR) group. Demographic data were collected from medical records. Biochemical parameters were measured using routine methods. Genotypes of the interleukin-10 (IL-10), annexin A5 (AnxA5), and tumor necrosis factor-alpha (TNFα) loci were determined using real-time polymerase chain reaction and a high-resolution melting assay.Results:Fasting blood glucose, serum triglycerides, and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were higher in the ISR group than in the NISR group (P < 0.05), and a history of diabetes mellitus was significantly related to the presence of restenosis (P < 0.001). There were no significant differences in the frequency of the genetic polymorphisms of IL-10, AnxA5, and TNFα genes and the presence of ISR.Conclusion:After adjustment for clinical variables, the genetic polymorphisms at the IL-10, TNFα, and ANXA5 gene loci do not appear to be risk factors for >50% ISR in our population. However, our data suggested a significant association between diabetes mellitus, serum hs-CRP, stent type, and restenosis.

Influence polymorphism of genes interleukin-10 (1082G/A; rs1800896) and tumor necrosis factor-α (308G/A; rs1800629) on risks of developing adverse clinical forms of community-acquired pneumonia in young men

The influence of the structural polymorphism of the interleukin-10 genes (1082G/A; rs1800896) and tumor necrosis factor-α (308G/A; rs1800629) on the risk of adverse clinical forms of community-acquired pneumonia in young men has been evaluated. In patients with community-acquired pneumonia in young men, the GG genotype of the gene for interleukin-10 (1082G/A; rs1800896) and the AA and AG genotypes of the tumor necrosis factor-α gene (308G/A; rs1800629) have been found to be associated with a severe and prolonged course of this diseases. AA and AG genotypes of the tumor necrosis factor-α gene (308G/A; rs1800629) are associated with the complicated course of community-acquired pneumonia in young people. It was revealed that in young men, in the presence of the GG genotype of the interleukin-10 gene (1082G/A; rs1800896), the relative risk of developing severe disease increases by 3,2 times and the risk of developing long-term community- acquired pneumonia increases by 2,7 times. If young patients suffering from community-acquired pneumonia, AA or AG, have the genotype of the tumor necrosis factor-α gene (308G/A; rs1800629), the relative risk of developing severe course increases by 3,3 times, prolonged course - by 2,6 times, and complicated course - 1,9 times. The results of the study should be used in the diagnosis of community-acquired pneumonia in order to predict the development of adverse clinical forms. Interleukin-10 gene polymorphism (1082G/A; rs1800896) and tumor necrosis factor-α (308G/A; rs1800629) are individual typological features of a person, the verification of which is relevant for use in the diagnosis of community-acquired pneumonia in young people to predict development adverse clinical forms of the disease.

Association of interleukin-1 gene polymorphism with risk of gastric and colorectal cancers in an Iranian population.

Chronic inflammation is associated with neoplasms and several types of cancer. Therefore, polymorphisms in the inflammation-related genes could modify the cancer susceptibility. To investigate the associations between IL-1RN VNTR and rs419598 polymorphisms in IL-1 receptor antagonist (IL-1ra) and colorectal cancer (CRC) and gastric cancer (GC) in an Iranian population. In this study, 126 cancer cases (91 CRC and 35 GC) and 97 healthy controls were included. Genotyping of IL-1RN VNTR and rs419598 was performed by PCR amplification and PCR-RFLP, respectively. Logistic regression was applied to identify the independent risk factors for colorectal and gastric cancers by computing the odds ratio (OR) and 95% confidence intervals (95% CI). All statistical analyses were performed using the SPSS statistical software. There were significant differences between cancer groups and control group concerning the frequency of A1/A2 genotypes in IL-1RN VNTR polymorphism. The carrier status of IL-1RN* 2 allele was associated with increased risk of CRC (p = 0.0003; OR = 0.02; 95% CI: 0.491-0.85) and GC (p = 0.0006; OR = 0.106; 95% CI: 0.321-0.035). Also, the homozygous ILRN *2/*2 genotype was associated with increased risk of gastric cancer (p = 0.04; OR = 0.133; 95% CI: 0.020-0.908). There was no association between different alleles of rs419598 and CRC and GC. This study demonstrates an association between the carrier status of IL-1RN* 2 and CRC and GC in an Iranian population.

Течение муковисцидоза у детей в зависимости от мутаций генов-модификаторов воспаления интерлейкина-4 и интерлейкина-10

Течение муковисцидоза у детей в зависимости от мутаций генов-модификаторов воспаления интерлейкина-4 и интерлейкина-10