Interleukin-10 Polymorphisms Research Articles

Evaluation of interleukin 10, interleukin 1-beta, and tumor necrosis factor-alpha gene polymorphisms in patients with periodontitis and healthy controls

BackgroundChronic periodontitis (CP) is a prevalent infectious disease caused by an interplay between pathogens and immune responses. Gene polymorphisms are among the factors that affect susceptibility to CP. This study aimed to assess the association between CP and single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) genes.MethodsA total of 87 patients with CP and 89 healthy controls were included in this study. Venous blood samples were obtained, and DNA was extracted and purified. Segments containing the relevant genes were amplified by polymerase chain reaction (PCR). Electrophoresis was performed after restriction fragment length polymorphism (RFLP) to determine genotype and allele frequencies.ResultsThe CP group showed significantly different allele and genotype frequencies for three out of five SNPs: IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, and IL-1ß + 3954 C/T (p < 0.05). Additionally, the frequency of the TNF-α ─ 857 AA genotype was significantly lower in patients compared with controls (p = 0.034); however, no significant differences were found in allele frequencies (p > 0.05). Logistic regression analysis revealed that carriers of IL-10 ─ 592 A allele and IL-1ß + 3954 T allele are at higher risk of CP (p < 0.001). Allele and genotype frequencies for TNF-α ─ 308 G/A did not differ significantly between patients and controls (p > 0.05).ConclusionsThis study showed specific genotypes of IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, IL-1ß + 3954 C/T, and TNF-α ─ 857 G/A SNPs may be associated with an increased risk of CP development.

Gene polymorphisms of interleukin 10 (− 819 C/T and − 1082 G/A) in women with ovarian cancer

BackgroundOvarian cancer (OC) is the leading cause of death associated with gynecologic cancer. IL-10 plays an important role in tumorigenesis. We investigated IL-10 gene polymorphisms in OC patients. The current case–control study screened forty-eight women with OC and forty-eight healthy women who did not have OC. The genotyping of SNPs (− 1082 G > A; rs1800896 and − 819 C > T; rs1800871) of the IL-10 gene was done by tetra primers sequence-specific primer polymerase chain reaction (SSP-PCR) technique. The plasma levels of IL-10 were measured using an enzyme-linked immunosorbent assay (ELISA).ResultsFor IL-10 (− 1082 G/A) polymorphism, the G (wild allele) was significantly associated with increasing the risk of OC (OR = 2.054 with CI = 1.154–3.657; P < 0.05), while the A (variant allele) and AA genotype was significantly associated with decreasing the risk of OC (OR = 0.487 with CI = 0.273–0.867; P < 0.05) and (OR = 0.15; 95% CI = 0.04–0.63; P < 0.05), respectively. For IL-10 (− 819C/T) polymorphisms, the T allele (variant allele) and (TT, CT genotypes) were significantly associated with increasing the risk of OC (OR = 2.800 with 95% CI = 1.577–5.037; P < 0.05), (OR = 18.33 with 95% CI = 3.46–97.20; P < 0.001), and (OR = 9.44 with 95% CI = 2.52–35.40; P < 0.001), respectively, while the C (wild allele) was significantly associated with decreasing the risk of OC (OR = 0.357 with 95% CI = 0.199–0.642; P < 0.05). The haplotype analysis for (− 1082 G > A and − 819 C > T shows the GT haplotype was significantly associated with increasing the risk of OC (OR = 50.09 with CI = 6.34–395.92; P < 0.001). OC was substantially correlated with IL-10 level (r = 0.457; p < 0.001). There is no linkage disequilibrium (LD) between IL 10 − 1082 G/A and IL 10 − 819 C/T (D′ = 0.1315, r2 = 0.016; P = NS). A statistically significant positive relationship existed between IL-10 and CA125 and ALT (P < 0.05). IL-10 and albumin showed a strong negative association (P < 0.05), whereas the correlation of IL10 plasma level with BUN, AST, T. Bil., TLC, PLT, Cr., and HB has not any significant value (P > 0.05).ConclusionsOverall, this study supports an association of IL-10 (− 1082 G/A and − 819C/T) polymorphisms with the risk of ovarian cancer.

An interleukin-1 polymorphism additionally intensified by atopy as prognostic factor for aseptic non-mechanical complications in metal knee and hip arthroplasty.

In contrast to infection or mechanical issues joint replacement failure following inflammatory adverse reactions is poorly understood. To assess the association of IL-1β polymorphisms and history of allergy with aseptic non-mechanical complications following arthroplasty. In 102 patients with aseptic non-mechanically caused symptomatic knee or hip arthroplasty (SA) and 93 patients with asymptomatic arthroplasty (AA) questionnaire-based history, patch test with at least standard series, lymphocyte transformation test (LTT) with nickel, cobalt and chromium and interleukin-1 polymorphism analysis were done. Three polymorphisms of the IL1B gene [IL-1b -3954 (rs1143634), IL-1b -511 (rs16944) and IL-1b -31 (rs1143627)] and one polymorphism of the IL1RN gene [IL1RN intron 2, variable number of tandem repeats, VNTR (rs2234663)] were assessed by PCR and gel electrophoresis. We found no significant difference in smoking history and atopy but 25% versus 10% of self-reported metal allergy in SA versus AA; the patch test (respective, LTT) for metal sensitivity was more often positive in SA patients. The allele 498 bp of the IL1RN polymorphism occurred significantly more often in the SA group (37% versus 11%; p < 0.0001). Upon additional presence of atopy, the difference was even greater (60% vs 10%) (p < 0.000001). There was no association of IL-1 polymorphisms with metal allergy. The IL1RN VNTR allele 498 bp was strongly associated with SA. In patients with a history of atopy, presence of the IL1RN VNTR allele 498 bp led to a four-fold higher SA prevalence compared to patients without this allele.

Association of Single-Nucleotide Polymorphisms in Interleukin Genes with Microbial Keratitis in a South Indian Population

To examine the relationship between single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes and keratitis and its clinical manifestations. SNPs in IL1B, IL6, CXCL8, IL10, and IL12B were analysed. Differences in frequencies of alleles, genotypes and haplotypes between cases and controls as well as associations between SNPs and clinical variables were calculated by χ2 tests with odds ratios. The minor homologous genotype in IL1B rs16944 (p = 0.036; odds ratio (OR) = 2.063, 95% confidence interval (CI): 1.048-4.061) and CXCL8 rs4073 (p = 0.041; OR = 0.463, 95% CI: 0.224-0.956) and the heterologous genotypes in IL6 rs1800795 (p = 0.046; OR = 0.563, 95% CI: 0.326-0.972) and IL12B rs2569254 (p = 0.0446; OR = 0.557, 95% CI: 0.314-0.989) or rs730691 (p = 0.0051; OR = 0.451, 95% CI: 0.260-0.784) were associated with keratitis. The minor genotype of rs16944 was associated with severe infection (p = 0.046). The heterologous genotype in rs2569254 was associated with hospital admission, photophobia, and mode of contact lens wear (p ≤ 0.041). The heterologous genotype in rs730691 was associated with blurred vision, discharge, anterior chamber reaction, and mode of wear (p ≤ 0.047). This study demonstrates that SNPs in IL1B and CXCL8 are associated with risk of developing keratitis. The study also found relationships between SNPs and clinical measures of keratitis. The potential for ethnic differences in frequency of SNPs and their association with keratitis should be followed up using different populations.

Interleukin-10 promoter variability is associated with the susceptibility, severity, and clinical outcomes of aplasitc anemia in Han-Chinese population.

Acquired aplastic anemia (AA), a heterogeneous bone marrow (BM) failure disease, is mainly mediated by the immune destruction of hematopoietic stem cells (HSCs). Given the predominant role of immunosuppressive therapy (IST) in AA, it is sensible to theorize that variants of cytokine genes might affect the outcome of IST. In this study, we analyzed three single nucleotide polymorphisms (SNPs) of interleukin (IL)-10 gene in promoter region to clarify their relationship with susceptibility, clinical efficacy and prognosis of AA. We observed that CT genotype of IL-10 rs1800896 was associated with a decreased risk of AA (adjusted OR=0.541 [95% CI 0.295-0.993], p=.047). Besides, the disease severity differed considerably by IL-10 gene promoter genotypes and alleles. Furthermore, IL-10 SNPs influenced efficacy of IST, with unfavorable response exhibited by rs1800871 and rs1800872 in dominant models (GG + AG vs. AA, adjusted OR=0.409 [95% CI 0.178-0.943, p=.036] for rs1800871 and GG + GT vs. TT, adjusted OR=0.396 [95% CI 0.173-0.909, p=.028] for rs1800872, respectively). The polymorphisms of IL-10 promoter region were informatively genetic risk factors which might be conducive to the insights into the mechanisms of AA and the design of individual regimens.

Association of rs1800795 and rs1800796 polymorphisms in interleukin-6 gene and osteoarthritis risk: evidence from a meta-analysis

Multiple studies have investigated the association of interleukin-6 (IL-6) gene polymorphisms and osteoarthritis (OA) risk, but failed to reach a consistent conclusion. Therefore, this study was designed to elucidate the association of IL-6 polymorphisms and OA by a meta-analysis approach. Literature retrieval was carried out on PubMed, EMBASE, Web of Science, CNKI, and Wanfang databases. The strength of association was appraised by odds ratios (ORs) and 95% confidence intervals (95%CIs) in five genetic models. The data were merged by using RevMan 5.3 software. Ten studies with 4944 cases and 4651 controls were analyzed. Overall, no significant association was identified between rs1800795 polymorphism and OA. Subgroup analysis by ethnicity and OA site also suggested rs1800795 polymorphism was not associated with OA. For rs1800796 polymorphism, G-allele and GG-genotype carriers appeared to have an increased risk to OA (G vs. C, OR = 1.66, 95%CI 1.30-1.96, P < 0.01; GG vs. CC, OR = 1.75, 95%CI 1.07-2.84, P = 0.03; GG vs. GC + CC, OR = 1.82, 95%CI 1.42-2.34, P < 0.01). Findings of this study indicate that the rs1800795 polymorphism is not correlated to OA susceptibility, regardless of ethnicity or OA site. However, rs1800796 polymorphism trends to be associated with susceptibility to OA.

Association of interleukin-18 promoter polymorphism with comorbid conditions of cardiovascular disease

ObjectivesCardiovascular disease (CVD) is one of the most clinically relevant pathologies that remains the largest single contributor to global mortality. It is often associated with more than one comorbid condition, which obscures its clinical outcome. The current study aimed to evaluate the possible association of interleukin-18 (IL-18) promoter polymorphism with comorbid conditions of CVD. MethodsWe used case-control comparison of specific genotypes of three clinically relevant IL-18 polymorphism hotspots, viz. −656 T/G (rs1946519), −607C/A (rs1946518), and −137 G/C (rs187238) with commonly associated comorbid conditions of CVD such as diabetes, hypertension, and dyslipidemia. For this study, whole blood of CVD patients and healthy control subjects were collected in a citrate coated/plain tube. The routine biochemical parameters were estimated in each sample, and DNA samples were extracted for PCR amplification for further sequencing of targeted amplicons using Sanger method. ResultsThe studied biochemical parameters showed a significant increase in CVD patients compared with control individuals. Fasting glucose and glycosylated hemoglobin (HBA1C) showed an increase from 4.82 to 8.6 (p < 0.05) and 4.33 to 8.2 (p < 0.05), respectively. The results showed a statistically significant association with CVD-diabetes and CVD-hypertension group with GG, GC, and CC genotype at IL-18 gene locus, rs187238. On the other hand, the CVD-dyslipidemia group showed a positive association with allele distribution at the same hotspot. In addition, the GG, GT, and TT genotype and G and T allele distribution at rs1946519 locus showed statistically significant association with CVD-diabetes, CVD-hypertension, and CVD-dyslipidemia p compared with control subjects. We also observed a statistically significant association of dyslipidemia with three genotypic combinations viz. (rs1946518 AA, rs1946519 GG, rs187238 GG); (rs1946518 AA, rs1946519 GT, rs187238 GG), and (rs1946518 AA, rs1946519 TT, rs187238 GG). ConclusionsBased on our study, we conclude that IL-18 loci, rs1946519 has a significant association with each studied comorbid condition and can be considered a prognostic marker of CVD and comorbidities. Our results are anticipated to be utilized to launch a significant pharmaco-genomic investigation that could identify patients with comorbidities who are more likely to develop CVD.

Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese.

Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.

Association of Interleukin-6 Polymorphisms with Schizophrenia and Depression: A Case-Control Study.

Growing evidence suggests a crossover in genetic susceptibility to schizophrenia and depression. We aimed to investigate the association of the rs1800795 and rs1800796 polymorphisms of the IL-6 gene with schizophrenia and depression in the Han Chinese population, combined with IL-6 serum levels. Gene sequencing and enzyme-linked immunosorbent assay were performed on 113 subjects with schizophrenia, 114 subjects with depression, and 110 healthy controls. Our findings showed that IL-6 concentrations in schizophrenia and depression groups were significantly higher than in the control group. The rs1800796 CC genotype and C allele were significantly associated with depression (P = .012 and P < .05, respectively). The rs1800796 CC and CG genotype was significantly associated with chronic schizophrenia (P = .020 and P = .009, respectively). Regarding the rs1800795 polymorphism, only one case of CG genotype was detected. The remainder were of the GG genotype. The IL-6 rs1800796 might serve as a protective factor for depression and schizophrenia in the Han Chinese population.

Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis.

Hepatocellular carcinoma (HCC) is the most common liver malignancy. Early diagnosis of HCC has always been challenging. This study aims to assess the pathogenicity and the prevalence of IL-6 -174G/C (rs1800795) and TGFβ-1 +29C/T (rs1800470) polymorphisms in HCV-infected HCC patients. Experimental strategies are integrated with computational approaches to analyse the pathogenicity of the TGFβ-1 +29C/T and IL-6–174 G/C polymorphisms in HCV-induced HCC. AliBaba2 was used to predict the effect of IL-6–174 G/C on transcription factor binding site in IL-6 gene. Structural changes in the mutant TGFβ-1 structure were determined through project HOPE. To assess the polymorphic prevalence of IL-6 -174G/C and TGFβ-1 +29C/T genotypes in HCC and control subjects, amplification refractory mutation system PCR (ARMS-PCR) was performed on 213 HCC and 216 control samples. GraphPad Prism version 8.0 was used for the statistical analysis of the results. In-silico analysis revealed the regulatory nature of both IL-6 -174G/C and TGFβ-1 +29C/T polymorphisms. ARMS-PCR results revealed that the individuals carrying TT genotype for TGFβ-1 gene have an increased risk of developing HCC (p<0.0001, OR = 5.403, RR = 2.062) as compared to individuals with CT and CC genotype. Similarly, GC genotype carriers for IL-6 gene exhibit an increased risk of HCC susceptibility (p<0.0001, OR = 2.276, RR = 1.512) as compared to the people carrying the GG genotype. Genotype TT of TGFβ-1 gene and genotype GC of IL-6 gene are found to be associated with HCV-induced HCC. IL-6 polymorphism may alter its transcription that leads to its pathogenicity. TGFβ-1 polymorphism may alter protein structure stability.

Role of Interleukin-6 Polymorphism in Acute Graft-Versus-Host Disease Risk Prediction in Allogeneic Hematopoietic Stem Cell Transplantation

BACKGROUND: This study aimed to determine the association of single-nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6) gene with the survival and disease status of patients after allogeneic hematopoietic stem cell transplantation. MATERIALS AND METHODS: It was a prospective cohort study of total 102 participants, 51 patients along with their donors who had human leukocyte antigen-identical-matched allogeneic hematopoietic stem cell transplantation (aHSCT). Their pretransplant and posttransplant blood samples were collected for extraction of DNA for genotyping by sequence-specific primers polymerase chain reaction and gel electrophoresis followed by sequencing. The pre- and posttransplant levels of IL-6 were measured using enzyme-linked immunosorbent assay technique. RESULTS: The mean age of our patients was 19.83 ± 12.5 years having males 65 (63.7%) and females 37 (36.3%). The frequency of −174G/C SNP among acute graft-versus-host disease (aGVHD) group was GG = 53.8%, GC = 34.6%, and CC = 11.5%, and for −597G/A SNP, it was GG = 69.2%, GA = 15.4%, and AA = 15.4%. Our results showed that the presence of G allele in both homozygous and heterozygous forms was associated with increased aGVHD incidence, while the homozygous CC and AA mutant genotypes correlated with the lowest number of cases of aGVHD. The polymorphism −597G/A was significantly associated with the incidence of aGVHD with P = 0.04. The GG genotype in −174G/C and −597G/A was found to be significantly associated with aGVHD with P &lt; 0.0001. High serum levels of IL-6 pre- and posttransplant were found to be significantly associated with the incidence of aGVHD with P &lt; 0.0001. CONCLUSION: We concluded that the two SNPs − 174G/C and − 597G/A in the promoter region of IL-6 gene present either in donors or recipients predisposed to increase the risk of development of aGVHD following aHSCT. Their evaluation in our transplant setting may help in the risk stratification of transplant recipients early in time and predict the onset of aGVHD and mortality.

Exploring the association of interleukin polymorphisms with aggression and internalizing behaviors in children and adolescents.

There is growing evidence that inflammation influences mental health. Blood interleukin levels, which regulate inflammation, have been linked to aggression and internalizing behaviors. We performed a hypothesis-driven genetic study to (1) evaluate the association of IL1B, IL2, and IL6 gene variants with aggression and internalizing behaviors and (2) explore gene-environment interactions with childhood adversity in a deeply phenotyped childhood-onset aggression sample including 255 cases and 226 controls of European ancestry. We evaluated the association of putative functional and tag SNPs within IL1B, IL2, and IL6 with aggression case status, parent-reported internalizing problems, self-reported anxiety symptoms, and self-reported depressive symptoms in our sample. We also performed exploratory GxE analyses within cases, testing for statistical interaction between interleukin SNP genotype and childhood adversity for depressive symptoms. No significant association was observed between any of the interleukin SNPs and childhood-onset aggression. We observed association of IL6 variant rs2069827 with depressive symptoms (p=7.15×10-4 ), and trends for an interaction between severe childhood adversity and SNPs in IL1B and IL2 for depressive symptoms. Our findings provide preliminary evidence that common variation in IL6 may be associated with depressive symptoms in children and adolescents, and that common variation in interleukin genes may sensitize individuals to the depressogenic effects of traumatic life experiences. Replication in independent samples is needed.

The association of Interleukin-10 and Interleukin-13 polymorphisms with susceptibility to vitiligo: A study in Iranian patients

Vitiligo is an autoimmune disease with non-pigmented and pale white patches in skin. Different studies showed that cytokines play a role in the onset of vitiligo symptoms. The aim of the present study was to investigate the association of IL-10 and IL-13 polymorphisms with susceptibility to vitiligo. With this aim, DNA was extracted from peripheral blood of 90 patients with vitiligo and 90 healthy individuals. Then, the genotype of IL-10 (rs1800896 T > C and rs1800872 T > G) and IL-13 (rs2069756 T > C and rs1295685 G > A) polymorphisms was determined by PCR-RFLP. The results of statistical analysis indicated that the heterozygote genotype of rs1800872 as well as rs2069756 significantly decreased the susceptibility to vitiligo (p < 0.05). However, no association was observed between rs1800896 and rs1295685 polymorphisms and the risk of vitiligo (p > 0.05). Among the patients, the heterozygote genotype of rs1800872 polymorphism showed to be associated with increased risk of Acrofacial phenotype development (p < 0.05). The obtained results suggested that heterozygote genotype of rs1800872 and rs2069756 polymorphisms play a protective role against development of vitiligo (p < 0.05). However, the heterozygote genotype of rs1800872 could be stated as a susceptible factor for onset of Acrofacial phenotype in patients with vitiligo.

Association of IL-6 genotypes with their serum levels among Iraqi patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a complex autoimmune system disease and significant impact on the health of the population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. Interleukin-6 (IL-6) is a common pro-inflammatory cytokine that has several roles in a variety of pathophysiologic systems, most notably in the development of rheumatoid arthritis (RA). This study aims to investigate the association of polymorphism of the “IL-6 174 G/C rs(1800795) gene” to their serum levels among Iraqi patients. A total of 60 participants (40 confirmed rheumatoid arthritis patients and 20 controls) were selected using a convenient sampling method. “Genetic polymorphism of IL-6 174 G/C rs(1800795)” was carried out using RFLP-PCR. Serum levels of IL-6 were performed using by enzyme-linked immunosorbent assay technique (ELISA) using a Human- IL-6 kit. Based on the polymorphism of IL-6 174 G/C rs(1800795), serum levels of IL-6 were higher among rheumatoid arthritis patients with CC and GC genotypes than that with GG genotypes (CC, 137.5336±35, GC 135.0622±70.88476and GG 65.5587±1.77873, P &lt; 0.05. Furthermore, patients with GG genotype had the lowest IL-6 level with an insignificant difference compared to controls1. 65.5587±1.77873vs. 59.8203±1.30673,P&gt; 0.05.

Association of interferon gamma inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha, interleukin-6, and rs12252 single nucleotide polymorphism of interferon-induced transmembrane protein-3 gene with the severity of COVID-19 infection

BackgroundEvaluating the serum levels of IP-10, MCP-1, MIP-1α, and IL-6 and genotyping of rs12252 SNP of IFITM3 gene among different categories of COVID-19 patients might aid in understanding the pathogenesis of COVID-19 and contribute to developing disease-specific biomarkers and therapeutic strategies.MethodsThis is a cross-sectional study involving a total of 84 COVID-19 patients confirmed by positive RT-PCR and 28 healthy controls. COVID-19 patients were recruited from the intensive care unit (ICU) and COVID unit of Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka. COVID-19 patients were categorized into moderate, severe, and critically ill groups according to the World Health Organization classification. The serum IP-10, MCP-1, and MIP-1α levels were measured by cytometric bead array assay by flow cytometry, and serum IL-6 level was detected by the chemiluminescence method. rs12252 SNP of the IFITM3 gene was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP).ResultsThe serum IP-10, MCP-1, MIP-1α, and IL-6 levels among critically ill COVID-19 patients were significantly higher than that in patients with moderate disease and healthy controls (p < 0.001). Genotype distribution for rs12252 (42 T/C) SNP of the IFITM3 gene between the different groups of COVID-19 patients and healthy controls showed that CC genotype was statistically associated with disease severity (p < 0.001).ConclusionsIP-10 and MCP-1, MIP-α, IL-6, and CC genotype of rs12252 (42 T/C) SNP of IFITM3 gene are associated with COVID-19 severity.

Association between interleukin 10 (IL-10) polymorphisms and leishmaniasis progression: a systematic review and meta-analysis

Interleukin 10 (IL-10) is associated with the progression of leishmaniasis because it inhibits the leishmanicidal action of macrophages and the production of mediators such as IFN-γ and nitric oxide. Studies have shown that specific polymorphisms are associated with the regulatory role of IL-10 and the development of more relevant clinical forms of leishamaniasis. We performed a systematic review and meta-analysis to determine whether single nucleotide polymorphisms (SNPs) of IL-10 influence the progression of leishmaniasis. The selected articles were read in full and only those consistent with the eligibility criteria were included in our study. Seven studies were eligible according to the inclusion criteria and were included in the present systematic review, but only five were subjected to statistical analysis. The pooled odds ratios showed no significant association between the rs1800871 SNP and the progression of leishmaniasis in all genotype models, including the dominant, recessive, homozygote, heterozygote, and allelic models. Regarding the association between rs1800896 SNP and the progression of leishmaniasis, the pooled odds ratios showed no association under all genotype models. Hence, IL-10 SNPs did not show significant association and were not considered a risk factor for the progression of leishmaniasis.

PB1967: ROLE OF CYTOKINES IN MULTIPLE MYELOMA: IL-1RN AND IL-4 VNTR POLYMORPHISMS

Background: Cytokines have important effects on immune regulation and oncogenesis. IL-1 is a cytokine with important physiological roles in cytokine regulation, vascular permeability and sepsis in autoimmune diseases. The IL-1 receptor antagonist (IL-1Ra or IL-1RN) is a member of the IL-1 superfamily that functions as a competitive antagonist of the cell surface IL-1 receptor, thereby regulating various immune and inflammatory responses related to IL-1. IL-1 induces tumor growth and metastasis, while IL-1RN inhibits the secretion of IL-1α and IL-6 in cancer cells. Interleukin-4 (IL-4) is a potent anti-inflammatory cytokine, and its gene is located on the long arm of chromosome 5 (q23-31) along with other cytokine genes. IL-4 can be secreted by many types of immune cells, including basophils, eosinophils, myeloid lineage cells, mast cells, and activated T cells. Aims: In this study, it was aimed to reveal the effects of IL-1RN and IL-4 VNTR polymorphisms on disease development and survival in patients with MM. Methods: In this study, 244 patients diagnosed with MM in hematology clinic between January 2010 and January 2021, and 179 healthy individuals were included. The control group did not have any kind of cancers and consisted of a unrelative population permanently residing in Turkey. ASCT was performed for 73% of the patients after 4 courses of VCD (bortezomib, cyclophosphamide, and dexamethasone) with at least a partial remission and then LD (lenalidomide and dexamethasone) was used as a maintenance therapy for the following follow-up period. The 1/1, 1/2, 1/3, 1/4, 2/2, 2/3 and 2/4 genotypes of the IL-1RN VNTR polymorphism were statistically compared before treatment between patients having undergone ASCT and healthy controls, as were the 1/1, 1/2 and 2/2 genotypes of IL-4 VNTR polymorphism. Additionally, the statistically significant effects of these genotypes on survival were examined. Results: The median age of 244 patients included in the study was 58 old years (range: 29-81). The 5-year and 10-year OS were 76% and 53%. The 5-year and 10-year PFS were 42% and 21%, respectively. The median PFS was 42,3 months. The median follow-up period was 27 months (4,4-155 months). In the statistical analysis of the distribution of IL-1RN VNTR gene variants, 1/3 and 1/4 genotypes were found to be significantly higher in patients with MM compared to the healthy controls (p=0,035). In the statistical analysis of the distribution of IL-4 VNTR gene variants, there was no significant difference between the MM patient group and the healthy controls in terms of genotype distribution (p>0.05, for all). IL-4 VNTR genotype distribution did not have a significant effect on PFS and OS. PFS of patients with IL-1RN VNTR non-2-allele carrier genotypes was significantly shorter, but no significant effect was found on OS (p=0,03, p=0,786, respectively. Patients with IL-1RN VNTR non-2-allele carrier genotypes had 1,718-fold increased risk of shorter PFS. Image:Summary/Conclusion: In conclusion, with this study, the effects of IL-1RN VNTR and IL-4 VNTR polymorphisms on MM were evaluated for the first time in the literature. The IL-1RN 1/3 and 1/4 genotypes were significantly more common in patients with MM compared to healthy controls. Patients with IL-1RN VNTR non-2-allele carrier genotypes had 1,718-fold increased risk of shorter PFS, but no significant effect on OS was demonstrated. IL-4 polymorphism, on the other hand, did not have a significant effect on MM development or survival. This study will shed light on ones on cytokine-MM relationship and epigenetic mechanisms.

Association of CTLA-4 and IL-4 polymorphisms in viral induced liver cancer

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent types of cancer and is responsible for close to one million annual deaths globally. In Pakistan, HCC accounts for 10.7% of cancer incidence. Prior studies indicated an association between interleukin 4 (IL-4) and cytotoxic T lymphocyte protein 4 (CTLA-4) gene polymorphisms in many types of cancers, including HCC that are either hepatitis B virus (HBV)- or hepatitis C Virus (HCV)-induced. The association of IL-4 and CTLA-4 genetic polymorphisms with HCV-induced HCC is not yet determined in the Pakistani population. Therefore, this research is designed to investigate the implication of IL-4 and CTLA-4 gene polymorphisms by determining the association of IL-4 -590 C/T (rs2243250) and CTLA-4 + 49 A/G (rs231775) with HCC in Pakistan.MethodsDifferent bioinformatics tools were employed to determine the pathogenicity of these polymorphisms. Samples were collected from HCV-induced HCC patients, followed by DNA extraction and ARMS-PCR analysis.ResultsThe SNP analysis results indicated a positive association of IL-4 -590C/T and CTLA-4 + 49A/G gene polymorphisms with HCV-induced HCC in Pakistan. The CTLA-4 polymorphism might enhance therapeutic efficiency of HCC chemotherapy medicines. The IL-4 polymorphism might introduce new transcription factor binding site in IL-4 promoter region.ConclusionThis study delineated risk factor alleles in CTLA-4 and IL-4 genes associated with HCV-mediated HCC among Pakistani patients that may have application to serve as genetic markers for pre- and early diagnosis and prognosis of HCC in HCV patients.

Association between interleukin-1, interleukin-6, and tumor necrosis factor-alpha polymorphisms and juvenile idiopathic arthritis: a meta-analysis.

In juvenile idiopathic arthritis (JIA), interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are associated with development and progression of JIA. We investigated whether IL-1, IL-6, and TNF-α polymorphisms were associated with susceptibility to JIA. A meta-analysis was conducted on the associations between IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA (PubMed and Embase). A total of 27 studies involving 4678 JIA patients and 7634 controls were considered in the meta-analysis. There was no association between the IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA in allele contrast or any other genetic models. In subgroup analysis based on subtype, except for the dominant model of TNF-α-238 G/A, systemic JIA was not significantly associated with IL-6 and TNF-α polymorphisms. In Caucasians, the dominant and additive models of IL-1β-511 C/T were significantly associated with JIA (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.09-2.00, P=0.01; OR 1.46, 95% CI 1.05-2.03, P=0.02, respectively). This meta-analysis showed no association between IL-1, IL-6, and TNF-α polymorphisms, and JIA, but the TT genotype of IL-1β -511 C/T was associated with higher prevalence of JIA in Caucasians.

INTERLEUKIN-16 RS4778889 POLYMORPHISM AND ITS INTERACTION WITH INTERLEUKIN-10 RS1800896 POLYMORPHISM INCREASE THE RISK FOR KNEE OSTEOARTHRITIS IN THE LEBANESE POPULATION

To investigate the effect Interleukin-16 (IL-16) and Interleukin-10 (IL-10) polymorphisms, and their interaction, on knee osteoarthritis (KOA) risk in the Lebanese population. Kompetitive Allele Specific PCR (KASP) genotyping assay was performed to determine IL-16 rs4778889, rs11556218, and rs4072111 and IL-10 rs1800896 polymorphisms in 118 patients diagnosed with KOA ( ≥ 2 points on Kellgren-Lawrence (K&amp;L) radiological classification scale) and 70 controls matched for age and gender (K&amp;L score ≤ 1). After adjusting for age, gender, presence of metabolic disorders, smoking and drinking status, our findings suggest that rs4778889 TT genotype increases the risk for KOA compared to the combined CC and TC genotypes (OR=2.131, 95% CI 1.037 – 4.379, p = 0.04) and that the T allele increases KOA risk compared to the C allele (OR=1.8, 95% CI 1.008 – 3.212, p = 0.047). No significant associations with the disease risk were found for the other studied polymorphisms (p &gt; 0.05). Our data suggest that there is an interaction between IL-16 rs4778889 and IL-10 rs1800896 (p = 0.010). IL-16 rs4778889 TT genotype increases the risk for KOA only among individuals carrying IL-10 rs1800896 GG or GA genotypes (OR=4.821, 95% CI 1.847 – 12.583). None of the IL-16 haplotypes was associated with KOA risk in our study population (p &gt; 0.05). Our findings suggest that IL-16 rs4778889 T allele is associated with KOA and that there is an interaction between this polymorphism and IL-10 rs1800896 with regard to KOA.