Interleukin-10 Gene Research Articles

Investigating the interplay of hematological parameters, CD markers, genetic polymorphisms, and database mutations in the IL15 gene in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by the clonal expansion of myeloid precursor cells in the bone marrow. In this study, we investigated the interplay of hematological parameters, CD markers, genetic polymorphisms, and database mutations in the interleukin 15 (IL15) gene in AML patients. We enrolled 59 newly diagnosed AML patients and analyzed their bone marrow specimens using flow cytometry and molecular techniques. The hematological parameters of the AML patients revealed a significant increase in platelet count and RBC, Hb, and HCT levels compared to healthy individuals. CD marker expression analysis revealed upregulation of CD33, CD45, CD13, CD117, CD38, HLA-DR, CD15, CD64, MPO, CD34, and CD11c in AML patients. Molecular analysis showed 15 mutations in different positions of exon 8 of the IL15 gene, with the most frequent mutation being a homozygous mutation resulting from a nucleotide substitution. Additionally, 10 novel heterozygous mutations were identified in different locations of chromosome 4, with a low variant rate. Finally, database analysis of gnomAD and Mutagene revealed a high number of potential driver mutations in the IL15 gene in leukemia patients. These results provide valuable insights into the genetic and immunophenotypic characteristics of AML patients and highlight the potential role of IL15 in AML pathogenesis.

IL10 Gene and Neurodegenerative Sclerosis: A Systematic Review and Meta-Analysis

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are incurable degenerative scleroses with unclear etiology. Neuroinflammation is an important factor in the neurodegeneration characteristic of these diseases. Additionally, Interleukin 10 (IL10) can inhibit the synthesis of inflammatory cytokines and plays a protective role against neurodegeneration associated with neuroinflammation. Thus, we developed a systematic review and meta-analysis in order to clarify the relationship between polymorphisms in the IL10 gene and MS and/or ALS. We searched for observational studies in four international databases without time restrictions. Seventeen studies were added to the systematic review and six polymorphisms were observed: IL10-592 (rs1800872; C>A), IL10-819 (rs1800871; C>T), IL10-1082 (rs1800896; A>G), IL10-2763 (rs6693899; A>C), IL10-2849 (rs6703630; A>G) and IL10-3575 (rs1800890; A>T). In the meta-analysis, we used odds ratio (OR) and 95% confidence interval (CI) to evaluate the association of IL10-1082, IL10-819 and IL10-592 polymorphisms and MS. We found a positive association of MS with the IL10-1082 SNP in genotypic comparison (AG+GG vs. AA) (OR = 1.23; 95% CI = 1.01–1.51; p = 0.04). Our search did not find any article relating polymorphisms in the IL10 gene with ALS. Therefore, our analysis indicates a possible association of IL10 gene SNPs in the development and progression of MS.

Potential involvement of IL-32 in cell-to-cell communication between macrophages and hepatoblastoma.

This study investigated the expression of interleukin 32 (IL-32) in hepatoblastoma, the most common primary pediatric liver tumor, and its possible roles in tumorigenesis. IL-32 expression was investigated in two hepatoblastoma cell lines (Hep G2 and HuH 6) in the steady state and after co-culture with macrophages by RNA-seq analysis and RT-qPCR, and after stimulation with chemotherapy. Cultured macrophages were stimulated by IL-32 isoforms followed by RT-qPCR and western blot analysis. IL-32 immunohistochemical staining (IHC) was performed using specimens from 21 hepatoblastoma patients. Clustering analysis was also performed using scRNA-seq data downloaded from Gene Expression Omnibus. The IL-32 gene is expressed by hepatoblastoma cell lines; expression is upregulated by paracrine cell-cell communication with macrophages, also by carboplatin and etoposide. IL-32 causes protumor activation of macrophages with upregulation of PD-L1, IDO-1, IL-6, and IL-10. In the patient pool, IHC was positive only in 48% of cases. However, in the downloaded dataset, IL-32 gene expression was negative. IL-32 was detected in hepatoblastoma cell lines, but not in all hepatoblastoma patients. We hypothesized that stimulation such as chemotherapy might induce expression of IL-32, which might be a critical mediator of chemoresistance in hepatoblastoma through inducing protumor activation in macrophages.

Correlation analysis of IL-37 gene polymorphisms and susceptibility to chronic HBV infection among Han people in Central China.

Hepatitis B virus (HBV) is responsible for various liver diseases, such as chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis (LC) and hepatocellular carcinoma (HCC), which pose a significant threat to human health. An ineffective immune response to HBV can result in viral chronicity. Interleukin-37 (IL-37), an immunomodulator, is capable of inhibiting both innate and adaptive immune responses. It is believed that single nucleotide polymorphisms (SNPs) within the IL-37 gene could contribute to the regulation of HBV clearance. Our aim to conduct this study was to investigate whether SNPs in the IL-37 gene were associated with the risk of chronic HBV infection in adults. A total of 342 participants, consisting of 171 cases and 171 controls, were recruited for this study. Sanger sequencing was employed for genotyping six SNPs (rs3811042 G/A, rs3811043 G/C, rs2466449 A/G, rs3811045 C/T, rs3811046 T/G and rs3811047G/A). There was no significant difference in allele and genotype distribution between the two groups, and the constructed haplotypes were not found to be associated with the risk of chronic HBV infection. Our results revealed that there was no relationship between these six SNPs (rs3811042G/A, rs3811043G/C, rs2466449A/G, rs3811045C/T, rs3811046T/G and rs3811047G/A) in the IL-37 gene and susceptibility to chronic HBV infection among Han people in Central China.

Association of Interleukin-6 and Tumor Necrosis Factor-alpha Gene Polymorphisms with Gnetic Susceptibility of Psoriatic Arthritis in Kuwaiti Arab Patients

Background: Psoriatic arthritis (PsA) is an inflammatory arthritic disease in which joint inflammation occurs with psoriasis. It results from a complex interplay between genetic, immunological and environmental factors. In PsA, the activation of T cells is considered as a crucial step in the disease process. The T-lymphocytes affect the proliferation of epidermal skin cells and result in abnormal differentiation. Altered cytokine networks have been shown to play a central role in the pathogenesis of PsA. Psoriasis is characterized by Th-1 type cytokine pattern in which there is a marked variation in the secretion of interleukin-6 (IL6), interleukin-13 (IL13) and Tumor necrosis factor-alpha (TNF-alpha). This study investigated the association of IL6, IL13 and TNF-alpha gene polymorphisms with genetic susceptibility of PsA in Kuwaiti patients. Methods: The genotypes of IL6 gene (-174G/C; rs1800795), IL13 gene (R130Q; rs20541) and TNF-alpha gene (-308A/G’ rs1800629) polymorphisms were detected in 113 Kuwaiti PsA patients and were compared to that in 104 healthy controls. The PsA patients were diagnosed on the basis of the presence of inflammatory arthritis with psoriasis with no rheumatoid factor in the serum. The genotypes for IL6, IL13 and TNF-alpha gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods and were confirmed by DNA sequencing. Results: The frequency of IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G’ rs1800629) polymorphisms manifested a statistically significant difference between Kuwaiti PsA patients and controls. However, the frequency of IL13 gene (R130Q; rs20541) polymorphism did not show a significant difference between Kuwaiti PsA patients and the controls. Conclusion: Our data show an association of two cytokine gene polymorphisms in IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G’ rs1800629) with PsA in Kuwaiti patients highlighting their significant contribution to genetic susceptibility of this chronic disease possibly along with other factors.

IL-10 (−1082 G/A) polymorphism in Bataknese with schizophrenia

ObjectivesThree biallelic polymorphisms at the promoter region of the interleukin-10 (IL-10) gene have been associated with susceptibility to schizophrenia. The aim of this case-control study was to investigate the association between IL-10 (−1082) G/A gene polymorphisms and schizophrenia among Bataknese, a native tribe inhabiting the North Sumatera province in Indonesia. MethodsA total of 194 unrelated participants (n = 97 for each case and control groups) participated in this study. Polymerase chain reaction restriction fragment length polymorphism molecular genotyping was conducted to assess the genotype and allele distribution of IL-10 (−1082 G/A). ResultsAllele variations indicated that the dominant allele in the Batak tribe was allele A, whereas homozygous GG genotypes were not found in either group. The A allele and AA genotype were found to be risk factors for developing schizophrenia (OR = 2.26, 95% CI = 1.1825–4.3559 and OR = 2.56, 95% CI = 1.280–5.152, respectively). ConclusionOnly the A allele and AA genotype of the IL-10 gene polymorphism at −1082 G/A contribute to schizophrenia susceptibility in Bataknese.

Effects of upadacitinib and PD29 on oxidative damage and inflammation in bleomycin-induced scleroderma model kidney tissues

Objective: Scleroderma (SSc) is a rare autoimmune tissue disease. There is currently no effective treatment for SSc. The aim of this
 study was to investigate the antioxidant and anti-inflammatory effects of upadacitinib and PD29 on total oxidant status (TOS), total
 antioxidant status (TAS), malondialdehyde (MDA), catalase (CAT), glutathione (GSH) peroxidase levels, and interleukin-6 (IL-6) and
 interleukin-13 ( IL-13) in kidney tissues of an experimental SSc model.
 Materials and Methods: The experimental design was established with five groups of eight mice: Control, bleomycin (BLM) (5 μg/kg),
 BLM + upadacitinib (3mg/kg), BLM + PD29 (5 mg/kg) and BLM + PD29 + upadacitinib group. BLM was administered subcutaneously
 once a day for 21 days. PD29 was administered subcutaneously and upadacitinib (gavage) were injected for 21 days. Renal tissues were
 collected at the end of the experiment. Renal TOS, TAS, MDA, CAT, GSH levels, and IL-6 and IL-13 gene expressions were evaluated.
 Results: Upadacitinib and PD29 affected oxidant status and TOS. MDA levels decreased, and GSH, CAT, and TAS levels increased.
 Also, upadacitinib and PD29 decreased inflammation via IL-6 and IL-13 cytokines.
 Conclusion: Upadacitinib and PD29 may have therapeutic roles for SSc renal crisis.

Screening of IL-22 first and second introns and FOXP3 second exon for SNPs and mutations with potential role in the susceptibility of SLE in selected population.

The main objective of performing this study was the mutational analysis of Forkhead box family member (FoxP3) and Interleukin-22 (IL-22) genes and their associations with systemic lupus erythematosus (SLE). A total of sixty blood samples were collected from SLE patients from different hospitals in Lahore. Proforma was based on American College of Rheumatology (ACR) criteria. The total time for this research was one year (2018-2019). DNA was extracted, and FoxP3 and IL-22 genes were polymerized through PCR and further sequenced through the Sanger Sequencing method. Chromas version 2.6.6 was used for the similarity index of sequences. NG_060763 and NG_007392.1 were used as Reference Sequences of IL-22 and FoxP3 genes, respectively. Three already identified Single Nucleotide Polymorphisms (SNPs) in the IL-22 gene i.e., rs2227491, rs2227485, and rs2227513, were confirmed in the sequencing results of SLE patients. Results showed that there were nine novel mutations (27.27%) in the case of the IL-22 gene in the studied genotyped samples. These SNPs had remarkably increased allele T frequency in rs2227485 and allele C frequency in rs2227491 and rs2227513. On the other hand, in the case of FoxP3 gene exon 2, there was an addition of T at position 10 in the intronic portion, thus not involved in the progression of the disease. The importance of cytokine-mediated signaling pathways, such as the IL-22 gene, is thus established. Novel variants in the IL-22 gene likely contributed significantly to the development of this autoimmune disorder. The current study found that the dysregulation of the inflammatory markers in SLE is not related to the FoxP3 gene, even though FoxP3 is implicated in the tolerance process.

Gene expression of Interleukin-10 and Foxp3 as critical biomarkers in rheumatoid arthritis patients

Introduction and Aim: Forkhead box P3 (FOXP3) and interleukin-10 (IL-10) are the key regulators controlling the activity of Treg cells, which are crucial for maintaining immune tolerance and reducing autoimmune reactions. The objective of this study was to investigate the potential utility of elevated levels of FOXP3 and IL-10 gene expression as a diagnostic indicator in patients with rheumatoid arthritis (RA). Materials and Methods: The study used quantitative polymerase chain reaction (qPCR) to examine the expression levels of FOXP3 and IL-10 transcripts in whole blood samples from Iraqi patients with rheumatoid arthritis. A group of healthy control subjects were also included in the study. Results: In blood samples taken from Iraqi patients diagnosed with rheumatoid arthritis, a statistically significant decrease (P 0.01) in the expression levels of the FOXP3 gene and a statistically significant elevation (P 0.01) of IL-10 expression were seen in contrast to the healthy control group. Conclusion: Rheumatoid arthritis patients in Iraq may benefit from FOXP3 and IL-10 gene expression tests. IL-10 and FOXP3 overexpression promotes T cell and immune system immunoreactivity.

Interleukin-18, Interleukin-18 Gene Polymorphisms and Interleukin18 Binding Protein in Children and Adolescents with Immune Thrombocytopenia

Background Immune thrombocytopenia (ITP) is an autoimmune illness characterized by an aberrant T cell response, which is supported by autoreactive B cell growth and differentiation. IL-18 expression has been linked to a number of autoimmune and inflammatory illnesses. IL18BP is a protein that binds IL-18 with high affinity, suggesting a potential mechanism for regulating IL-18 activity. Corticosteroids may play a significant role in reversing the IL-18- IL18BP ratio by upregulating IL18BP. Objective The aim was to study associations between IL-18 and two associated gene polymorphism sites -607 & -137 with incidence and response to therapy in patients with ITP. Patients and Methods It is a case control study conducted on children and adolescents with ITP.A total of 55 patients with different stages of ITP (25 acute, 18 persistent & 12 chronic patients) were recruited with 30 age matched healthy controls. All patients were subjected to full history and physical examination. Laboratory investigations included serial blood counts, IL-18 and IL-18BP serum levels using enzyme linked immunosorbent assay (ELISA) and IL-18 gene polymorphisms using polymerase chain reaction (PCR). Results At diagnosis the median platelet count was 16× 109/L (range 2-79) & eventually increased to a median of 90× 109/L after treatment. IL-18 level was significantly higher than that of control (P < 0.001) & even after treatment. There was no significant difference between patient and control groups regarding the studied gene polymorphism sites -607 & -137. The mean IL-18 was still significantly elevated in all stages of ITP compared to control group & as well the drop after treatment. This was also observed in IL-18 BP which increased significantly after response to steroid therapy. However, it was observed that the decline in level of IL-18 as well as increment in IL-18 BP was the least in the patients tested during the acute phase. Mean IL-18 & IL-18 BP levels show no significant relation with gender, family history of ITP, mode of treatment or genotype. Conclusion Among the studied IL-18 gene polymorphisms, no significant difference was detected among ITP patients or had a significant correlation with clinical or laboratory markers. Reversed IL-18/IL-18BP ratio is an important modulator in pathogenesis of ITP. Increasing levels of IL-18BP could have a significant role in treatment.

Association of IL-10 Gene in Protection Against COVID-19 Disease

Background: The medical community is facing a new challenge with the coronavirus disease 2019 (COVID-19) pandemic, as the severity of the disease is largely determined by the overexpression of proinflammatory cytokines, leading to endothelial dysfunction and organ damage, especially in the lungs. Objectives: It is believed that mutations might be linked to severe illness. This cross-sectional study aimed to explore the correlation between COVID-19 severity in Iranian pediatric patients who were referred to Namazi Hospital (Shiraz, Iran) and interleukin 10 (IL-10) gene polymorphisms (rs1800896, rs1800871, and rs1800872). Methods: The study comprised 53 pediatric patients with COVID-19, who were divided into mild/moderate (n = 44) and severe (n = 9) groups. Nasal swabs and whole blood samples were collected from each patient who participated in the study. Real-time polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmation (E, RdRp) and PCR-restriction fragment length polymorphism (RFLP) were used for IL-10 gene polymorphism genotyping. Results: The study investigated the association between IL-10 gene polymorphisms and COVID-19 severity in pediatric patients. The results showed that the GA genotype at the IL10-1082 locus was protective against severe symptoms and that all severe cases were male with the AA/GA genotype. The other two loci, IL10-819 and IL-10-592, did not show any significant association with COVID-19 severity. The study also showed that shortness of breath was the only symptom significantly associated with COVID-19 severity and that age and gender did not affect the disease outcome. Conclusions: The most common symptoms in the mild/moderate group were cough and fever; however, shortness of breath and cough were the most common in the severe group. Coronavirus disease 2019 severity is related to the IL-10 (rs1800872) gene polymorphism, with the GA genotype providing protective effects.

Lowered IL-37 gene expression and elevated IL-37-producing tissue-resident immune cells in psoriasis lesional biopsies.

Psoriasis is an immune cell-dependent chronic autoimmune skin disorder. Interleukin 37 (IL-37) is a cytokine belonging to the IL-1 family that shows anti-inflammatory and protective effects in various mouse models of psoriasis. Even though various animal models are used to investigate the pathogenic mechanisms of psoriasis, human clinical studies are still needed to make up for the deficiencies, as animal models generally do not exhibit the complex phenotypic features of human psoriasis. Our study aims to demonstrate the relationship between IL-37-producing tissue-resident immune cells with the pathogenesis of psoriasis. The present study was performed on 28 psoriasis patients and 17 healthy volunteers. The ability of anti-inflammatory cytokine IL-37 to impede inflammation and regulate metabolic pathways was assessed by real-time quantitative polymerase chain reaction. Finally, immunofluorescence double staining for CD4+ IL-37b+ , CD68+ IL-37b+ , and (forkhead box protein P3) Foxp3+ IL-37b+ was performed. The proportion of CD4+ IL-37b+ T cells, CD68+ IL-37b+ macrophages, and Foxp3+ IL-37b+ T regulatory (Treg) cells was significantly increased in the psoriasis group compared to the control group. IL-37 gene expression was downregulated in psoriasis when contrasted to the control group. Our findings disclosed that IL-37-producing tissue-resident immune cells might be involved in the pathogenesis of psoriasis, and thus may be a therapeutic target for individuals with psoriasis.

Interleukin 10 (IL-10) gene variants and haplotypes in Tunisian women with polycystic ovary syndrome (PCOS): a case-control study.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women in their child-bearing age, and is associated with insulin resistance and type 2 diabetes. The etiology of PCOS involves multiple factors including genetic, metabolic and immunological factors. Interleukin - 10 (IL-10), as an anti-inflammatory cytokine, plays a critical role in this regard. We investigated the potential role of IL-10 gene variants in the development of PCOS in Tunisian population. 115 cases and 120 controls were recruited in the current case control study. Rotterdam consensus criteria were used to diagnose PCOS patients. Genotyping for IL-10, rs1800896, rs1800871 and rs1800872 variants, was performed by real time PCR. The results obtained showed that the minor allele frequency of rs1800896, rs1800871and rs1800872 were comparable between PCOS cases and control subjects (P = 0.30, P = 0.71, and P = 0.57 respectively). The distribution analysis revealed an unsignificant association of the three tested variants, in all genetic models. Haplotype analysis identified one haplotype CCA with a protective role in PCOS development (P = 0.05; OR (95% CI) = 0.56 (0.32 - 0.99)). This association did not persist after adjustment for multiples covariates (Pc = 0.154). Our study is the first to show how ethnicity influences the association of IL-10 gene variants with PCOS susceptibility. No allelic nor genetic association were observed between the tested variants and PCOS in Tunisian women, however, a particular IL-10 haplotype with a protective effect for PCOS was identified.

Correlation of Interleukin-21 Levels With Clinical and Laboratory Parameters in ART Recipients

Background: Interleukin-21 (IL-21) is a relatively new immune-enhancing, multifunctional and pleiotropic cytokine that plays an essential role in controlling chronic viral infections. It is a protein that in humans is encoded by IL-21 gene, mapped on chromosome 4 and 180 kb from IL-2 gene and the mRNA encoding the product is 616 nucleotides long. IL-21 is expressed in activated human CD4+ T cells but not in most other tissues. In addition, IL-21 expression is up-regulated by Th2 and Th17 subsets of T helper cells, as well as T follicular cells. Further IL-21 is expressed in NKT cells regulating the functions of these cells. IL-21 may be a critical factor in the control of persistent viral infections such as HIV. Present study aims to explore the levels of IL-21 in a select segment of ART recipients of East Delhi covered by NACP, Govt. of India.
 Methods: Estimation of levels of IL-21 was done using ELISA test employing commercially available kit (QAYEE-BIO Kit for Interleukin-21). The method of ELISA used for the present study was sandwich ELISA.
 Results: The mean levels of IL-21 in the study of 40 ART recipients were 1178.21±927.063. There were no controls included in the study. The range of IL-21 were 150-6100. In one patient IL-21 levels was not detected.
 Conclusion: This study attempts a clinical correlation with the levels of a cytokine with clinical and laboratory parameters which could help in a better understanding of the immunobiology of the disease. In the current study, the levels of IL-21 in samples of ART recipients were detected. A significant positive clinical correlation was seen between the levels of IL-21 and CD4 cell counts. IL-21 levels were high in those patients whose CD4 cell count was raised. There was a positive correlation between CD4 cell count and CRP. Therefore, further studies with a higher sample size may be required to arrive at a statistically significant correlation

Associations between blood IL-33 levels and IL-33 gene polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis.

This study investigated the relationship between circulating interleukin-33 (IL-33) levels and systemic lupus erythematosus (SLE) along with polymorphisms in the IL-33 gene and SLE susceptibility. The MEDLINE, EMBASE, and Cochrane Library databases (to May 2023) were searched for relevant publications. Using a meta-analysis we investigated serum/plasma IL-33 levels in patients with SLE and controls, and the relationship between IL-33 rs1929992, rs1891385, rs7044343, rs1095498, and rs10975579 polymorphisms and the risk of developing SLE. Nine studies focusing on 1,935 patients with SLE were included. IL-33 levels were significantly higher in the SLE group than in the control group (SMD = 2.140, 95% CI = 1.068-3.212, p < .001). Asian, European, and Arab groups have shown increased IL-33 levels in SLE populations, according to ethnic stratification. Regardless of the sample size, variable adjustment, data format, or publication year, the subgroup analysis showed significantly higher IL-33 levels in the SLE group. This meta-analysis supported the significance of the link between SLE and the IL-33 rs1891385 C allele (OR, 1.525; 95% CI, 11.310-1.777; p = .010). A similar association was found between the IL-33 rs1891385 C/A polymorphism and SLE, using homozygote comparisons and dominant and recessive models. However, this meta-analysis found no association between the IL-33 polymorphisms rs1929992, rs7044343, rs1095498, and rs10975579 and susceptibility to SLE. This meta-analysis identified significantly higher levels of circulating IL-33 in patients with SLE as well as an association between IL-33 rs1891385 and SLE.

IL-10 Polymorphism and Breast Cancer Risk in Georgian Women: A Case-Control Study.

Background Interleukin-10 (IL-10) is a cytokine with a vast variety of functions, but its role in cancer development and progression is not yet clear. It is involved in two of the hallmarks of cancer: vascularization and immune modulation. IL-10 inhibits angiogenesis and hence is antitumorigenic. But it also can suppress the immune system and be tumorigenic. Objective Evaluating the role of IL-10 (-1082 A/G) gene promoter single-nucleotide polymorphism (SNP) in breast cancer susceptibility and progression in Georgian women. Methods A case-control study was performed on a total of 128 women, with 64 of them being histologically confirmed to have breast cancer and 64 healthy controls. SNP genotyping was performed with TaqMan assay with real-time polymerase chain reaction. And pathology report, containing proliferative activity and breast cancer hormonal status, was obtained after surgery of the case individuals. Statistical analysis was done to investigate the significance of data obtained from genotyping and histology reports. Results Statistical analysis revealed that the difference in frequency of genotypes was not statistically significant between cases and controls (chi-square = 0.5812, p = 0.7478). The comparison of proliferative activity of cases with AA genotypes and AG/GG genotypes showed no statistical difference ( t = 0.2575, p = 0.7980). Although when put into a plot (box and whiskers), patients with AG/GG genotype have outliers with very high proliferative activity. Conclusion This study shows that -1082 A/G SNP in the promoter region of the IL-10 gene is not associated with breast cancer risk in Georgian women.

Association between interleukin-27 gene polymorphisms and Plasmodium falciparum Malaria.

Malaria is often characterized by a complicated disease course due to multifaceted intrinsic genetic factors of the host and the parasite. This study aimed to investigate the role of interleukin-27 (IL-27) gene polymorphisms in Plasmodium falciparum malaria infection in a Saudi Arabian cohort. This case-control study obtained blood samples from 250 malaria patients with P. falciparum and 200 randomly identified healthy control subjects from the Malaria Center in the Jazan area. Malaria patients were grouped into three cohorts as follow: low (<500 parasites/µl of blood), moderate (500-1000 parasites/µl of blood), and high (>1000 parasites/µl of blood) parasitemia. The results show that the IL-27 variant rs181209 was significantly associated with malaria patients (P = 0.026). Similarly, the homozygous GG genotype of rs26528 was also associated with risk of developing P. falciparum malaria (P = 0.032). The minor allele C of variant rs181206 exhibited an association with low to moderate parasitemia (P = 0.046). Furthermore, the rs181209 AA genotype was statistically significant in age group 1-5 years (P = 0.049). In conclusion, this study suggests that variant rs181209 and rs26528 could be associated with the risk of malaria infection by P. falciparum in the population studied.

IL18 Gene Polymorphism Is Associated with Total IgE in Adult Subjects with Asthma.

The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008-2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998-2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes.

Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children. Six candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA. The frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P < 0.001, OR = 2.79; AA vs. GG: P = 0.003, OR = 5.51; AG + AA vs. GG: P = 0.036, OR = 2.93; CAA vs. CAG: P = 0.001, OR = 2.86). Our findings suggested that genetic variation in IL-4 rs2243283 such as G allele, CG genotype and CG + GG genotype might confer the reduced susceptibility to AD in Chinese children. Furthermore, A allele, AA genotype and AG + AA genotype of IL-18 rs7106524 explored the strong association with severity in Chinese AD children.

Associations between circulating interleukin-17 levels and Behcet's disease and between IL-17 gene polymorphisms and disease susceptibility: a meta-analysis.

To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and Behçet's disease (BD) and the associations between polymorphisms in IL17 genes and BD susceptibility. We searched the Medline, Embase, and Cochrane databases for relevant articles. We performed a meta-analysis of serum/plasma IL-17 levels in BD patients and controls and evaluated the associations between IL17A rs4711998, rs8193036, and rs2275913 and IL17F rs763780 and rs2397084 polymorphisms and the risk of BD. Twelve studies, involving 901 patients with BD and 1,131 controls, were included. Our meta-analysis revealed that circulating IL-17 levels were significantly higher in the BD group than in the control group (SMD = 1.422, 95% confidence interval [CI] = 0.689-2.155, p<0.001). Subgroup analysis by data type indicated higher IL-17 levels in the BD group in both the original and calculated data populations. Stratification by publication year revealed significantly lower vitamin D levels in the SSc group in both recent and older publication years. No significant differences in IL-17 levels were observed between the active and inactive disease groups. We found no evidence of associations between BD and IL17A rs2275913, L17F rs763780, or rs2397084 polymorphisms. However, a significant association was found between BD and IL17A rs4711998 and rs8193036 polymorphisms in the pooled cohort of affected individuals compared to that in pooled controls (odds ratio [OR] = 1.347, 95% CI = 1.043-1.741, p<0.001; OR = 0.691, 95% CI = 0.542-0.880, p=0.003). This meta-analysis revealed significantly higher circulating IL-17 levels in BD patients and showed evidence of associations between IL17A rs4711998 and rs8193036 polymorphisms and BD.