IL-10 Genotypes Research Articles

Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis.

Background and objective: Inflammation and cell-mediated immunity can have significant roles in different stages of carcinogenesis. The present meta-analysis aimed to evaluate the association between the polymorphisms of IL-8 (-251T/A) and IL-6 (-174G/C) and the risk of oral cancer (OC). Methods: PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until December 18, 2020 without any restrictions. RevMan 5.3 software was used to calculate the results of forest plots (odds ratios (ORs) and 95% confidence intervals (CIs)); CMA 2.0 software was used to calculate funnel plots (Begg’s and Egger’s tests), and SPSS 22.0 was used for the meta-regression analysis. Moreover, trial sequential analysis was conducted to estimate the robustness of the results. Results: Eleven articles including twelve studies were selected for the meta-analysis. The pooled ORs for the association between IL-8 (-251T/A) polymorphism and the risk of OC in the models of A vs. T, AA vs. TT, TA vs. TT, AA + TA vs. TT, and AA vs. TT + TA were 0.97 (p = 0.78), 0.86 (p = 0.55), 0.78 (p = 0.37), 0.83 (p = 0.45), and 1.10 (p = 0.34), respectively. The pooled ORs IL-6 (-174G/C) polymorphism and the risk of OC in the models of C vs. G, CC vs. GG, GC vs. GG, CC + GC vs. GG, and CC vs. GG + GC were 1.07 (p = 0.87), 1.17 (p = 0.82), 1.44 (p = 0.38), 1.28 (p = 0.61), and 0.96 (p = 0.93), respectively. There was no association between IL-8 (-251T/A) polymorphism and OC susceptibility, but the C allele and GC and CC genotypes of IL-6 (-174G/C) polymorphism were associated with the risk of OC based on subgroup analyses, that is to say, the source of control and the genotyping method might bias the pattern of association. Conclusions: The meta-analysis confirmed that there was no association between the polymorphisms of IL-6 (-174G/C) and IL-8 (-251T/A) and the susceptibility of OC. However, the source of control and the genotyping method could unfavorably impact on the association between the polymorphisms of IL-6 (-174G/C) and the risk OC.

449 Periodontitis as a risk factor for psoriasis

Patients with psoriasis have an increased risk for inflammatory periodontal disease, however, data are sparse. Inflammatory disorders are well known to trigger psoriasis. We examined the periodontal status in 50 patients with psoriasis compared to 25 healthy control individuals. We examined whether there is (1) an enhanced periodontal risk, (2) increased IL-1 mediated inflammation, (3) increased bacterial load, (4) sufficient oral hygiene, and (5) an enhanced risk for tooth decay in psoriasis. Patients with psoriasis (19 female, 31 male) had a median age of 56 years, controls (17 female, 8 male) of 40 years. Individuals were given a questionnaire about general and dental health. Tooth and periodontal status was ascertained (perio-tools®, CA Ramseier, Univ. Berne, Switzerland). The DMFT-index (decayed, missing, filled teeth), BOP (bleeding on probing), PSI-Index (periodontal screening) were measured. Bacterial analyses from gingival pockets were done by micro-IDent ®/Hain Lifescience measuring 5 parodontal species by PCR. IL-1 gene variants were determined from buccal swabs/Hain Lifescience. Statistical analyses, t-test, U-test, Chi-square, Fisher’s exact test were done by SPSS 23 software. We found the following results: Psoriasis patients were smokers in 40% vs. 12% in controls (p<0.03). Interdental tooth cleaning was done in 38% of patients but in 80% of controls (p<0.001). There was no difference in cariogenic nutrition. Regular dentist visits were less frequent in psoriasis (64 vs. 96%). Gingivitis, tooth migration, tooth loss after loosening, gingival treatment did not differ. Missing, decayed or carious teeth were more frequent in psoriasis (10.3 vs. 6.4, p<0.013). DMFT-Index did not differ. Gingival pockets (>3.5 mm) were more frequent in psoriasis (85.4 vs. 60%, p<0.021). BOP did not differ. Bacterial growth occurred in 95.8% in psoriasis vs 72% in controls (p<0.006), specifically of the Tannerella forsythia-species (p<0.05). IL-1 genotype did not differ. Periodontal risk was significantly higher in psoriasis (48% vs. 25%, p<0.029). Our data indicate that periodontitis can be considered as a risk factor for psoriasis.

Cytokine gene polymorphisms in lymphoma: Thesis Abstract

Thesis Abstract Several cytokines are known to be involved in the pathogenesis of non-Hodgkin Lymphomas (NHL). Given the importance of understanding the genetic predisposition involved in the pathogenesis of NHL, this work was designed to study the impact of IL-10 (-1082 G/A; rs1800896 and -819 C/T; rs1800871), IL-6 (-174 G/C; rs1800795) and CD38 (184C/G; rs6449182) gene polymorphisms on the susceptibility of Egyptians to NHL. Both loci of IL10 were genotyped using polymerase chain reaction- sequence-specific primers (PCR-SSP), IL6 rs1800795 G/C was genotyped using mutagenically separated PCR (MS-PCR) and restriction fragment length polymorphism-PCR (RFLP-PCR) was used to genotype CD38 (rs6449182 C/G) in 100 Egyptian patients and 119 controls. Plasma levels of IL-6 and IL-10 were measured using enzyme-linked immunosorbent assay (ELISA). An insignificant change in IL-10 (rs1800896 and rs1800871) genotypes were recorded. GT haplotype was significantly elevated.

Association of IL-10 (\u2212\u20091082 A/G) and IL-6 (\u2212\u2009174\u2009G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population

BackgroundInterleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Therefore, this study aimed to assess IL-6 (− 174 G/C) and IL-10 (− 1082 A/G) gene polymorphism, and its association with T2DM, North West Ethiopia.MethodsA comparative cross-sectional study from January to May 2018 was conducted on study participants with T2DM and apparently healthy controls. Deoxyribonucleic acid (DNA) extraction and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction to detect polymorphism of IL-6 and IL-10 gene at the position − 174 and − 1082, respectively. The logistic regression model was fitted to assess the association of between cytokine gene polymorphisms and T2DM. Odds ratio with 95% CI was determined to assess the presence and strength of association between the explanatory variables and outcome variable. A P-value < 0.05 was considered as statistically significant.ResultParticipants carrying the GG genotype of IL-6 (− 174) (OR (95% CI) = 4.61 (2.07–10.54) was a high likelihood of having T2DM compared to those carrying the CC and AA genotypes. AA and AG genotypes of IL-10 (− 1082) were at lower odd of developing T2DM compared to those carrying the GG genotype. In addition, individuals carrying the G allele of IL-6 (− 174) have 2.82-fold odds of developing T2DM compared to individuals carrying the C allele (OR (95% CI) =2.81 (1.78–4.50)).ConclusionOur study revealed that genetic polymorphisms of IL-6 (− 174) GG genotype is the potential host genetic risk factors to T2DM. While, IL-10 (− 1082) AA genotype is negatively associated with T2DM. Therefore, IL-6 (− 174) and IL-10 (− 1082) genetic variation may be considered as a biomarker for early screening and diagnosis of T2DM.

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets.

Background“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities (h2) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown.MethodsSerum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (βFS, h2 ={(1 + 8rspouseβFS)0.5 − 1}/(2rspouse)) and offspring-parent regression slopes (βOP, h2 = 2βOP/(1 + rspouse)) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples.ResultsQuantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from βOP (Ptrend = 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from βFS (Ptrend = 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile.ConclusionHeritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences between CRP (rs1130864, rs1205, rs1800947, rs2794521, rs3091244), FGB (rs1800787), IL-6 (rs1800795, rs1800796), IL6R (rs8192284), TNF-α (rs1800629) and APOE genotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome or Staphylococcus aureus bacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.

Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma.

Simple SummaryNeuroblastoma (NB) presents diverse biological and clinical characteristics, from spontaneous regression to highly malignant and aggressive unfavorable tumors that condition the therapeutic failure of conventional treatments. The tumorigenesis of NB can be the result of different genetic variants, which can influence the clinical outcome, and the survival of patients who have metastatic tumors is low. The role of cytokines such as interleukin (IL)-6 has been described in the NB microenvironment promoting tumor progression and metastasis. Single nucleotide polymorphism (SNP)-174 G > C in IL-6 and -251 T > A and +781 C > T in IL-8 regulate the expression of these cytokines, and could be associated with the clinical outcome in patients with NB. Our objective was to evaluate the association of the genetic polymorphisms of IL-6 and IL-8, as well as the serum levels of these cytokines in patients with NB, as this will allow the genetic bases of NB to be characterized and understood, in order to predict the outcome of the disease and develop new therapeutic strategies.There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.

The Interleukin-6 (rs1800797) Variant in Healthy Individuals at Medan City, North Sumatera Province

The Interleukin-6/IL6 (rs1800797) variant play a role in several diseases pathogenesis. The frequencygenotype of IL6 (rs1800797) varied based on different race, ethnicity, and underlying character inpopulation. This study aimed to assess the frequency of genotype and allele of IL6 (rs1800797) in healthyindividuals at Medan city, North Sumatera Province Province and this study can be used as a reference indetermining of several diseases for further studies. Genotyping of IL6 (rs1800797) in the promoter regionusing polymerase chain reaction and restriction fragment length polymorphism method, analysis using FokIrestriction enzyme. This study showed that the genotype frequency of GG, GA, and AA were 95.8 %, 4.2%, and 0 %, respectively. The allele frequency of G and A were 97.9 % and 2.1 %, respectively. The resultsindicated that the homozygous wild-type (GG) of IL6 (rs1800797) was higher than the heterozygous mutant(GA) and there was absent of homozygous mutant (AA) in this population. The frequency of G allele alsohigher than A mutant allele.

Cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease

IntroductionInflammation associated with rheumatic heart disease (RHD) is influenced by gene polymorphisms and inflammatory cytokines. There are currently no immunologic and genetic markers to discriminate latent versus clinical patients, critical to predict disease evolution. Employing machine-learning, we searched for predictors that could discriminate latent versus clinical RHD, and eventually identify latent patients that may progress to clinical disease. MethodsA total of 212 individuals were included, 77 with latent, 100 with clinical RHD, and 35 healthy controls. Circulating levels of 27 soluble factors were evaluated using Bio-Plex ProTM® Human Cytokine Standard 27-plex assay. Gene polymorphism analyses were performed using RT-PCR for the following genes: IL2, IL4, IL6, IL10, IL17A, TNF and IL23. ResultsSerum levels of all cytokines were higher in clinical as compared to latent RHD patients, and in those groups than in controls. IL-4, IL-8, IL-1RA, IL-9, CCL5 and PDGF emerged in the final multivariate model as predictive factors for clinical, compared with latent RHD. IL-4, IL-8 and IL1RA had the greater power to predict clinical RHD. In univariate analysis, polymorphisms in IL2 and IL4 were associated with clinical RHD and in the logistic analysis, IL6 (GG + CG), IL10 (CT + TT), IL2 (CA + AA) and IL4 (CC) genotypes were associated with RHD. ConclusionDespite higher levels of all cytokines in clinical RHD patients, IL-4, IL-8 and IL-1RA were the best predictors of clinical disease. An association of polymorphisms in IL2, IL4, IL6 and IL10 genes and clinical RHD was observed. Gene polymorphism and phenotypic expression of IL-4 accurately discriminate latent versus clinical RHD, potentially instructing clinical management.

Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome.

Atrial fibrillation (AF) and cardiometabolic syndrome (CMS) have been linked to inflammation and fibrosis. However, it is still unknown which inflammatory cytokines contribute to the pathogenesis of AF. Furthermore, cardiometabolic syndrome (CMS) risk factors such as obesity, hypertension, insulin resistance/glucose intolerance are also associated with inflammation and increased level of cytokines and adipokines. We hypothesized that the inflammatory immune response is exacerbated in patients with both AF and CMS compared to either AF or CMS alone. We investigated inflammatory cytokines and fibrotic markers as well as cytokine genetic profiles in patients with lone AF and CMS. CMS, lone AF patients, patients with both lone AF and CMS, and control patients were recruited. Genetic polymorphisms in inflammatory and fibrotic markers were assessed. Serum levels of connective tissue growth factor (CTGF) were tested along with other inflammatory markers including platelet-to-lymphocyte ratio (PLR), monocyte-to-HDL ratio (MHR) in three groups of AF+CMS, AF, and CMS patients. There was a trend in the CTGF levels for statistical significance between the AF and AF+CMS group (P = 0.084). Genotyping showed high percentages of patients in all groups with high secretor genotypes of Interleukin-6 (IL-6) (P = 0.037). Genotyping of IFN-γ and IL-10 at high level showed an increase in expression in the AF + CMS group compared to AF and CMS alone suggesting an imbalance between the inflammatory and anti-inflammatory cytokines which is exacerbated by AF. Serum cytokine inflammatory cytokine levels showed that IL-4, IL-5, IL-10, IL-17F, and IL-22 were significant between the AF, AF+CMS, and CMS patients. Combination of both CMS and AF may be associated with a higher degree of inflammation than what is seen in either CMS or AF alone. Thus, the identification of a biomarker capable of identifying metabolic syndrome associated with disease will help in identification of a therapeutic target in treating this devastating disease.

Interleukin-6 (174G/C) Gene Polymorphism and Serum Levels of IL-6, their Association with Risk of Obesity in Iraqi Childhood Populations

Background: Childhood obesity is one of the most serious public health challenges of the 21st century.Aim: The present study was conducted to investigate the association of CD14 genotype and serum levels ofIL-6 with risk of ischemic stroke.Method : A total of 60 patients with obesity were included in the study who were admitted to hospital fromthe period between March to August 2020, and other groups consist of 60 apparently healthy individuals. Afive ml of blood samples were collected, 3 ml of each sample for polymerase chain reaction amplificationand detection of IL-6 technique. The remaining (2 ml) for IL-6 serum levels by ELISA assay procedure.Results: IL-6 (-174G/C) genotype was significantly associated with increased risk of obesity (P = 0.004).However, IL-6 serum levels were higher in subjects with GG genotype compared with those with CG or CCgenotype (P &lt; 0.001).Conclusion: A significant correlation between IL-6 genotype and IL-6 levels were higher level in subjectswith GG genotype compared with those with CG or CC genotype.

S0483 Cytokine Gene Polymorphisms in Irritable Bowel Syndrome vs Inflammatory Bowel Disease: A Network Meta-Analysis

INTRODUCTION: Cytokines are imbalanced in irritable bowel syndrome (IBS) and polymorphisms of cytokine-encoding genes may alter the risk of developing IBS. Whether IBS and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are separate entities or are on a spectrum with overlap is a question which has not been sufficiently explored. This study aimed to understand whether cytokine gene polymorphisms which are observed in IBS are also associated with IBD. METHODS: We designed a network meta-analysis to compare the distribution of three cytokine gene polymorphisms that have been more frequently studied in IBS and IBD: IL-10 (-1082GA), IL6 (-174GC), and TNF-α (-308GA). PubMed and Embase were searched for studies on the distribution of these polymorphisms in IBS and IBD vs. control. NetMetaXL (CADTH, Ottawa, Canada) was used for conducting this Bayesian network meta-analysis. Vague prior <0.5 suggested lower heterogeneity where fixed effects model was used. Odds ratio (OR) with 95% credible intervals [95% Cr.I.]. was used for the comparisons. RESULTS: Ten studies on IBS vs. controls, one on IBS vs. IBD vs. controls, and thirty-nine comparing IBD vs. controls, were included. The high producer IL-10 (-1082GG) genotype was less frequent in IBS vs. the three other groups: Controls 0.66 [0.50–0.88], UC 0.66 [0.47–0.91], and CD 0.72 [0.52–0.98]; while the intermediate producer IL-10 (-1082GA) was more frequently observed in IBS vs. Controls and UC. When comparing the low producer IL-10 (-1082AA) genotype in IBS with either IBD groups or Controls, no significant difference was observed, while CD had a lower frequency of IL-10 (-1082AA) vs. Controls. The high producer TNF-α (-308AA) was similarly distributed in IBS vs. other groups and was less frequent in Controls vs. UC: 0.68 [0.46–0.99]. TNF-α (-308 GG and GA) was similar among the study groups. IL6 (-174GC) was less frequent in IBS vs. CD: 0.73 [0.55–0.98]; and in UC vs. CD: 0.69 [0.53–0.89]. The high producer IL6 (-174GG) was less frequent in CD vs. UC: 0.73 [0.56–0.95]; while no difference was observed in IBS vs. other groups. CONCLUSION: IL-10 (-1082GA) has a more prominent role than TNF-α (-308GA) and IL6 (-174GC) in the pathogenesis of IBS and may distinguish IBS from IBD. There is a shift toward high producer pro-inflammatory TNF-α (-308AA) and IL6 (-174GG) in UC, distinguishing it from the other groups.

Interaction between and impact of IL-6 genotype and alpha-tocopherol levels on periodontal condition in aging individuals.

Few studies have assessed the possible interaction between and impact of IL-6 variants and serum α-tocopherol levels on periodontal condition in older individuals. Here, we assessed the relationship between IL-6 variants and serum α-tocopherol levels on periodontal condition by considering effect modification. Among the study participants, 359 who were 71years of age underwent a dental examination, biochemical analysis, and interview. After dividing the participants into tertiles based on serum α-tocopherol levels, we conducted Poisson regression analysis to compare the prevalence rate ratio (PRR) for periodontal disease markers with the IL-6 genotype (rs1800796) based on each tertile adjusted by the number of teeth present (offset). The PRRs of the IL-6 genotype for periodontal condition (probing pocket depth [PPD], clinical attachment level [CAL], and bleeding on probing [BOP]) which were adjusted by the number of teeth present (offset) were 1.17 (P<.001), 1.37 (P<.001), and 1.08 (P=.048), respectively. In addition, a significant association was found between the reciprocal number of PRRs of the IL-6 genotype and three serum α-tocopherol levels. The adjusted PRRs (± standard error) of the IL-6 genotypes for PPD were 0.48 (0.12) for the first group (P<.001), 1.54 (0.04) for the second group (P<.001), and 2.11 (0.03) for the third group (P<.001); similar tendencies were seen for CAL and BOP. The results of this study suggest a potential association between the IL-6 genotype and periodontal condition in relation to serum antioxidant concentrations.

Assessment of interleukin 6 gene polymorphisms with rheumatoid arthritis.

Rheumatoid arthritis (RA) is complex autoimmune system disease and significant impact on the health of population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. In this current study, we aimed to investigate IL-6 polymorphisms and RA risk in Chinese Han population. 508 RA patients and 494 age- and gender- matched healthy controls were recruited, all subjects were genotyped with an Agena MassARRAY platform. Subsequently, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjusting for age and gender. Our results suggested that IL-6 rs2243289 allele and genotype frequencies were associated with reduced RA risk under all genetic models (all p<0.05). Stratification analysis revealed that IL-6 rs2243289 polymorphism was significant associated with decreased the risk of RA in the old groups (age>54) (all p<0.05). However, IL-6 rs2069837 and rs1800796 polymorphisms were associated with increased risk of RA among the young groups (age≤54) (all p<0.05). In addition, subgroup analysis by gender suggested that IL-6 rs2069837 and rs1800796 polymorphism were interacted with increased the risk of RA in males (all p<0.05). Besides, IL-6 rs2243289 was associated with reduced RA risk in females. In conclusion, our results demonstrated the correlation between IL and 6 polymorphisms and RA susceptibility and confirmed for the first time that the relationship was restricted to age and gender in Chinese Han population.

ALL-232: Genetic Variants of Tumor Necrosis Factor α and Interleukin-10 in Childhood and Adult Acute Lymphoblastic Leukemia

Context Interleukin-(IL)10 and tumor necrosis factor (TNF) a have a significant role in malignancies. Genes encoding these cytokines are linked with different levels of gene transcription. Objective Analyzing IL-10 and TNFα gene polymorphisms and their contribution to ALL prognosis and survival. Design This prospective observational study was conducted from June 2017 until Oct 2019. Setting Oncology Center Mansoura University, Egypt. Patients or other participants We genotyped 64 children and 76 adult ALL patients for IL-10-1082A > G and TNFα-308G > A polymorphisms in the gene promoter region. We used polymerase chain reaction (restriction fragment length polymorphism method) for the molecular analysis. Results Pediatric ALL patients showed TNFα A allele and IL-10 A allele, which were associated with older age (p = 0.04, 0.03), extramedullary disease (p = 0.04, 0.001), and carried Philadelphia chromosome (p = 0.02, 0.001), compared to the G allele, respectively. IL-10-1082AA and TNF 308AA genotypes carried on the Ph-positive chromosome were associated with a longer time to CR and a higher rate of relapse than other genotypes. The IL-10 (GG) genotype was associated with significant improvement of OS compared to IL-10 (GA) and (AA) genotypes (p = 0.026). The adult ALL patients carrying the A allele of TNFα had a higher rate extramedullary disease (p = 0.009) and a higher rate of relapse (p = 0.003). Also, we found increased frequency of the IL-10-A allele with advanced age (p = 0.03), lower Hb level (p = 0.04), increased extramedullary disease (p = 0.001), and Ph chromosome positivity (p = 0.001), which resulted in longer time to CR (p = 0.003) and high relapse rate (p = 0.002). IL-10 (AA) and TNFα (AA) genotype patients were associated with extramedullary disease, carried the Ph-positive chromosomal abnormality, and had a higher rate of relapse than other genotypes among adult ALL patients. Patients with IL-10 (GG) and TNFα (GG) genotypes did not show significant improvement of OS and RFS by Kaplan-Meier curves (p > 0.05) compared to other genotypes. Conclusion IL-10 (AA) and TNFα (AA) were associated with poor prognostic factors in childhood and adulthood ALL. This might modulate the risk, overall survival, and relapse-free survival among ALL patients.

Association of IL-10 and TNF-\u03b1 polymorphisms with risk and aggressiveness of hepatocellular carcinoma in patients with HCV-related cirrhosis

BackgroundHepatitis C virus (HCV) infection is a significant risk factor for cirrhosis and hepatocellular carcinoma (HCC) that carry a high mortality. The study aims to investigate the effect of tumour necrosis factor (TNF)-α and interleukin (IL)-10 polymorphisms on risk and pattern of HCC in patients with HCV-related cirrhosis.ResultsThe mean age of the HCC group was 56.21 ± 4.62 years and 54.27 ± 7.63 years for the cirrhotic group. The GG genotype of TNF-ɑ and TT genotype of IL-10 showed a higher incidence of HCC in comparison to the cirrhotic group with P = 0.01 and 0.004. On the calculation of the aggressiveness index (AgI), the TT haplotype was significantly associated with more aggressive tumours in contrast to the other haplotypes with P < 0.001. There is a significant association of portal vein thrombosis, ascites and high AgI with the GG haplotype in contrast to the other haplotypes with P = 0.002, 0.029 and < 0.001, respectively, as regards TNF-α. High AgI (C) was associated with the TT haplotype of IL-10 and GG haplotype of TNF-ɑ.ConclusionOur data bring an essential association of IL-10 and TNF polymorphism with the occurrence of HCC in patients with HCV-related liver cirrhosis. The GG haplotype of TNF-ɑ and TT/AT haplotype of IL-10 are associated with the more aggressive pattern of HCC, so those patients must be treated as early as possible.

The Influence of −174 G/C Interleukin 6 Promoter Gene Polymorphism to Interleukin 6 Concentration in the End Stage Renal Disease Patients with Dialysis: A Single-center Experience in Indonesia

BACKGROUND: Chronic kidney disease (CKD) is classified as a multifactorial disease as a combination of genetic and environmental factors that affect the onset and progression of end-stage renal disease (ESRD). In the last decades are recognized that inflammation, where the critical modulator is cytokines, can occur before the onset of kidney disease and can be a causative factor in the development of CKD. Interleukin (IL)-6 has several polymorphisms in the promoter region, such as 174 G-C, 634 C-G, 572 G-C, and 597 G-A. G/C single nucleotide polymorphism of the IL-6 gene at position 174 in the promoter region is reported to affect the level of IL-6 expression. Unfortunately, there is a lack of data about the genotype frequencies of -174 G/C IL-6 promoter gene polymorphism in Indonesian with ESRD.&#x0D; AIM: This study aimed to analyze whether −174 G/C IL-6 promoter gene polymorphism influences the concentration of IL-6 in ESRD patients with dialysis in Indonesia.&#x0D; METHODS: We recruited 95 outpatients who were undergoing regular hemodialysis for ≥3 months at the Rasyida Renal Hospital, Medan, in this cross-sectional study. IL-6 genotype polymorphism was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay method was performed to assess the quantitative IL-6 serum.&#x0D; RESULTS: PCR-RFLP examination showed the frequency distribution of the IL-6 genotype -174 G/C gene; 72 (75.8%) respondents had GG genotypes; 22.1% of respondents had the CG genotype, and (2.1%) had the CC genotypes. Patients with the CC genotype were statistically significant to have higher IL-6 concentration compared to other genotypes (p &lt; 0.001). Likewise, with diabetic patients, statistics showed higher IL-6 concentration compared to non-diabetics patients (p &lt; 0.001).&#x0D; CONCLUSION: This is the first study showing that -174 G/C IL-6 promoter gene polymorphism influences the IL-6 concentrations in ESRD patients with dialysis in Indonesia. Multicenter studies are needed to validate these findings.

Association between TNFA, IL10 and IL18 promoter gene variants and cognitive functions in patients with relapsing-remitting multiple sclerosis

ObjectivesTo investigate the relationship between TNFA-308G > A, IL10–1082A > G, IL18-607C > A, and cognitive functioning in relapsing-remitting multiple sclerosis (RRMS). ResultsIn the patients' group: AG genotype of TNFA-308G > A was associated with higher serum tumor necrosis factor-alpha (TNF-alpha) than GG genotype, and higher TNF-alpha levels correlated with poorer results on Symbol Digit Modalities Test; CC genotype of IL18-607C > A was related to lower score on Isaacs test, compared to AC variant; AA genotype of IL10–1082A > G was associated with abnormally low results on Paced Auditory Series Addition Test. ConclusionsTNFA-308G > A, IL10–1082A > G and IL18-607C > A gene variants may be associated with impaired cognitive functions in RRMS patients.

Genetic Polymorphisms in Transforming Growth Factor-β, Interferon-γ and Interleukin-6 Genes and Susceptibility to Behcet's Disease in Saudi Population.

BackgroundBehcet’s disease (BD) is a complex, inflammatory, immune-mediated multi-systemic disease of unknown etiology. Cytokines play major roles in the pathophysiology of BD, and its production may be affected by polymorphism in cytokine genes. Hence, the present study was planned to investigate any possible association between the polymorphism in TGF-β, IFN-γ, and IL-6 genes and BD in the Saudi population.Materials and MethodsThe present study includes 79 BD cases and 117 age-matched controls. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation systems (ARMS) PCR methods were used for polymorphic analysis.ResultsThe heterozygous (CT) and (CT+TT) combined genotypes of TGF-β (509-C/T), heterozygous (AT), variant (TT), and (AT+TT) combined genotypes of IFN-γ (874-A/T) were significantly (P<0.05) associated with BD in the Saudi population. No significant differences were observed for IL-6 (174-G/C) genotypes and alleles between BD cases and controls. Gender does not reflect any significant genotypic and allelic association with males and females.ConclusionCT genotype of TGF-β, and AT and TT genotypes of IFN-γ could be associative genetic risk factors for BD in Saudis. Regulatory region polymorphism in cytokines gene can increase inflammation and deregulated immune response, which could be risk factor for BD.

Impact of IL-10 gene promoter -1082 (G/A) polymorphism in B cell chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among western population. Many interesting reports suggest the role of IL-10 polymorphisms in CLL oncogenesis. This study aimed to study the relation between IL-10 (rs1800896)-1082 (G/A) gene polymorphism and the risk of development of B cell chronic lymphocytic leukemia and its impact on the patient outcome. IL-10 (rs1800896)-1082 (G/A) gene polymorphism was assessed in fifty patients with chronic lymphocytic leukemia as well as 50 age and sex-matched apparently healthy controls using polymerase chain reaction (PCR). The IL-10 (rs1800896) AG hetero, GG homo, AG + GG genotypes, and G allele showed significantly higher frequency (P > 0.001) in CLL cases when compared to control groups. The genotype AG + GG were significantly associated with advanced stages (P > 0.001), short time to first treatment (TFT) (P = 0.032), shorter progression free survival (PFS) (P = 0.044), and lower response to treatment (P = 0.003) as compared to wild genotype (AA wild). The IL-10 (rs1800896) genotypes (GG, AG) might have a role in the pathogenesis of CLL and have deleterious impact on the CLL patient’s outcome.

Genetic Polymorphism of Il-16 and Risks of Coronary Artery Disease in Sudan

The inflammatory process in the atherosclerotic artery may lead to increased blood levels of inflammatory cytokines. The aim of this study is to understand the role of inflammatory markers in the development of coronary artery disease. Therefore, a case-control study was conducted amongst coronary artery disease patients who attended the Sudan Heart Institute and healthy controls. Questionnaires were designed to determine the lifestyle and environmental factors for 200 participants (100 cases, 100 controls). Blood samples were collected to measure lipids profiles using enzymatic colorimetric and DNA extraction using the G-spin Kits. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for IL-6 and IL-16 genotyping. A total of 64% patients were males, 41% were at 51-61 years, and physical activity was common in 60% of the patients. The risk factors for coronary artery disease were hypertension 62%, angina 62%, cigarette smoking 38%, diabetes 33%, tobacco user 31%, drinking alcohol 24% and stroke 2%. Most patients had a family history of stroke 93%, hypertension 36%, diabetes 34%, angina 9%, and heart attack 4%. Total cholesterol and low-density lipoprotein were significantly different (P&gt;0.05) between cases and controls, and they were significantly associated with IL-16 genotype. All risk factors for coronary artery diseases were strongly associated with IL-6 genotype (P-value &lt; 0.05, OR &gt;1). Whereas, IL-16 homozygous TT genotype was significantly associated with gender and physical activity. Lifestyle, family history, and IL-16 (TT) genotype are risk factors for coronary artery disease in Sudanese patients.