IL6 Rs1800795 Research Articles

Association of IL-4 rs2243250 polymorphism with susceptibility to tuberculosis: A meta-analysis involving 6794 subjects

BackgroundInterleukin-4 (lL-4) is a critical negative cytokine in tuberculosis (TB) immune process, acting through modulating macrophages activation and Th1/Th2 balance. rs2243250 has been demonstrated to be associated with enhanced promoter strength in IL-4 expression. We performed a meta-analysis to assess the association between IL-4 rs2243250 polymorphism and TB risk. MethodsWe identified relevant studies by a comprehensive search of PubMed, Web of Science, and Embase databases, published up to February 10, 2021. The pooled odds ratios (ORs) and its 95% confidential intervals (95%CIs) were used to evaluate the associations under five genetic models. All statistical analyses were conducted with STATA 12.0 software. ResultsTotally 11 qualified studies involving 3097 TB cases and 3697 controls were enrolled in this meta-analysis. Overall, we didn't detect any significant association between IL-4 rs2243250 polymorphism and TB risk (T vs. C: OR = 1.05, 95% CI = 0.85–1.30, p = 0; 65; TT + TC vs. CC: OR = 1.05, 95% CI = 0.73–1.50, p = 0.81; TT vs. TC + CC: OR = 1.10, 95% CI = 0.81–1.50, p = 0.54; TT vs. CC: OR = 1.17, 95% CI = 0.71–1.94, p = 0.54; TC vs. CC: OR = 1.03, 95% CI = 0.73–1.45, p = 0.88). Significant heterogeneity was identified in analyses under all genetic models. However, in the subgroup of European population, the recessive model provided an OR of 2.54 (1.30–4.96), with no significant between-study heterogeneity. ConclusionIn conclusion, our meta-analysis indicated that IL-4 rs2243250 may increase TB risk in European population in recessive genetic model. Further research is needed to clarify the cause of ethnic difference in genetic association study.

Association between idiopathic recurrent pregnancy loss and genetic polymorphisms in cytokine and matrix metalloproteinase genes.

Recurrent reproductive loss (RPL) is a global health issue affecting a significant number of women. Approximately half of miscarriages have an unexplained etiology. Familial aggregation and twins studies prove that some cases of the RPL could have a genetic background. Recent evidences suggest that cytokines (e.g. IL-6, TNF alpha or TGF beta) and matrix metalloproteinases (MMP) are important for maintenance of pregnancy. Single gene polymorphisms (SNP), affecting these proteins production or their function may predispose to the loss of the pregnancy. The aim of this study was to evaluate the association between the following polymorphisms of IL6 (rs1800795), TNF (rs1800629), TGFB1 (rs1800471), MMP1 (rs1799750), MMP2 (rs2285053 and rs243865), MMP3 (rs35068180), MMP9 (rs3918242) and the recurrent pregnancy loss in polish population. Study subjects comprised of 67 patients with a history of recurrent pregnancy loss (≥ 2 miscarriages in history) and 75 controls. The distribution of genotypes for selected polymorphisms were determined by RFLP-PCR. Maternal genotypes GG TNF, or 5A/5A MMP3 may be associated with the recurrent pregnancy loss. No association between the IL6, TGFB1, MMP1, MMP2, or MMP9 studied polymorphisms and the predisposition to miscarriage was found. This study demonstrated a possible association between rs1800629 TNF, rs35068180 MMP3 polymorphisms and recurrent pregnancy loss.

IL-4 rs2243250 polymorphism associated with susceptibility to allergic rhinitis: a meta-analysis.

Objective: The relationship between IL-4 rs2243250 polymorphism and the risk of allergic rhinitis is not clear at present. The present study aims to evaluate the exact association between IL-4 rs2243250 polymorphism and susceptibility to allergic rhinitis by a meta-analysis.Methods: The studies about IL-4 rs2243250 polymorphism associated with susceptibility to allergic rhinitis were searched using PubMed, Excerpta Medica Database (EMBASE), Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Wanfang databases. The last search time was on March 1, 2021. Data analysis was performed using Stata 15.0 software.Results: Nine documents were enrolled, from which 1709 patients with allergic rhinitis were included. Among them, six genotype frequencies in the control group conformed to Hardy–Weinberg Equilibrium (HWE). The meta-analysis of all included studies showed significant heterogeneity of each gene model. After omitting the studies whose genotype frequency in the control group did not meet the requirements of HWE, no significant heterogeneity was found in each gene model. The meta-analysis results of the control group genotypes in line with the HWE showed statistically significant differences in the pooled odds ratio (OR) of allele model (T vs. C), recessive model (TT vs. TC+CC) and homozygous model (TT vs. CC), which were 1.19 (95%CI: 1.04–1.35), 1.28 (95%CI: 1.06–1.55) and 1.56 (95%CI: 1.13–2.17), respectively. No statistically significant difference was observed in dominant and heterozygous genetic models.Conclusion: IL-4 rs2243250 single nucleotide polymorphism associated with susceptibility to allergic rhinitis, allele T and genotype TT could increase the risk of allergic rhinitis.

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.

IL-9 and IL-10 Single-Nucleotide Variants and Serum Levels in Age-Related Macular Degeneration in the Caucasian Population.

Considering the immunological impairment in age-related macular degeneration (AMD), we aimed to determine the associations of IL-9 rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884 and IL-10 rs1800871, rs1800872, and rs1800896 polymorphisms and their haplotypes, as well as the serum levels of IL-9 and IL-10 with AMD. 1209 participants were enrolled in our study. SNPs were genotyped using TaqMan SNP genotyping assays by real-time PCR method. IL-9 and IL-10 serum levels were evaluated using ELISA kits. Our study results have shown that haplotypes A-G-C-G-G and G-A-T-A-T of IL-9 SNPs are associated with the decreased odds of early AMD occurrence (p = 0.035 and p = 0.015, respectively). A set of rare haplotypes was associated with the decreased odds of exudative AMD occurrence (p = 0.033). Also, IL-10 serum levels were lower in exudative AMD than in controls (p = 0.049), patients with early AMD (p = 0.017), and atrophic AMD (p = 0.008). Furthermore, exudative AMD patients with IL-10 rs1800896 CT and TT genotypes had lower IL-10 serum concentrations than those with wild-type (CC) genotype (p = 0.048). In conclusion, our study suggests that IL-10 serum levels can be associated with a minor allele at IL-10 rs1800896 and exudative AMD. The haplotypes of IL-9 SNPs were also associated with the decreased odds of early and exudative AMD.

Association of IL-16 rs11556218 T/G polymorphism with the risk of developing type 2 diabetes mellitus.

Diabetes mellitus is a chronic disorder that has serious complications. Type 2 diabetes mellitus is more widespread worldwide and in Egypt. Interleukin-16 is a pro-inflammatory factor that can lead to many inflammatory diseases by stimulating the secretions of cytokines. Inflammation and obesity are concomitant factors that may lead to insulin resistance and type 2 diabetes mellitus. In this study, we tried to focus on the relation between Interleukin-16 rs11556218 polymorphism and the risk of development of type 2 diabetes mellitus. 128 type 2 diabetic patients and 128 healthy individuals as control were included in this case-control study. Interleukin-16 gene polymorphism (SNP rs11556218 T/G) was genotyped using a real-time polymerase chain reaction. Interleukin-16 rs11556218 T/G gene polymorphism has a statistically significant association with type 2 diabetes mellitus in the co-dominant, dominant and, over dominant genetic models. The genotype TG was presented in approximately 30 % of diabetic patients vs. control (p = 0.04) and patients with TG genotype have a 1.8 times higher risk for developing type 2 diabetes mellitus (OR1.87; 95 % CI = 1.04 to 3.39) and 9.5 times higher after risk-adjusted diabetes (OR9.58; 95 % CI = 1.50 to 61.25) (p = 0.031). We found an association between Interleukin-16 gene polymorphism with both body mass index and high density lipoprotein. This study is the first one in the Middle East and Africa which found a correlation between Interleukin-16 gene polymorphism rs11556218 and type 2 diabetes mellitus. Egyptians with TG genotypes have a higher risk to develop type 2 diabetes mellitus.

Interleukin-10 Gene Promoter Polymorphisms and Susceptibility to Asthma: Systematic Review and Meta-analysis.

Several studies have previously assessed the association betweeninterleukin (IL)-10gene polymorphisms and the risk of asthma, leading to conflicting results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis ofthe IL-10gene rs1800896, rs1800871, and rs1800872 single-nucleotide polymorphisms (SNPs) and susceptibility to asthma. A systematic literature search performed until April 2020, and the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to determine the association strength. Thirty articles comprising 5678 asthmatic patients and 6079 controls met the inclusion criteria. No significant association was found between rs1800872 SNP and susceptibility to asthma across all genetic models in the overall and subgroup analyses. The rs1800871 SNP had only significant association with a decreased risk of asthma in Europeans (OR 0.66, CI 0.53-0.82, P < 0.001). However, rs1800896 SNP was significantly associated with a decreased risk of asthma by dominant (OR 0.67, CI 0.50-0.90, P < 0.001) and heterozygote (OR 0.66, CI 0.49-0.88, P < 0.001) models in the overall analysis. Subgroup analyses indicated significant association of rs1800896 SNP by dominant (OR 0.45, CI 0.28-0.72, P < 0.001) and heterozygote (OR 0.43, CI 0.26-0.70, P < 0.001) models in the African population. The IL-10 rs1800896 SNP confers protection against the risk of asthma, especially in Africans. Additionally, rs1800871 SNP has a protective role against asthma in Europeans.

Pediatric Non-Alcoholic Fatty Liver Disease Is Affected by Genetic Variants Involved in Lifespan/Healthspan.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan-related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children. We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin-6 [IL-6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD-related metabolic and liver features in 177 pediatric patients with biopsy-proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case-control analysis of SNP-SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features. Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL-6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP-SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024). In conclusion, here we demonstrated a synergic interaction between IL-6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD-associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD.

Association of Genetic Polymorphisms in Oxidative Stress and Inflammation Pathways with Glaucoma Risk and Phenotype.

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.

The Association between IL2 Genotypes and Risk and Severity of Chronic Periodontitis in a Chinese Han Population: A Case-control Study

ABSTRACT Chronic periodontitis (CP) is a kind of multifactorial common oral diseases. Multiple immune molecules including interleukin-2 (IL-2) are involved in the occurrence and development of CP. To investigate the association between the IL2 rs2069762 polymorphism and the risk of CP in Chinese individuals, we recruited 375 CP patients and 443 controls in this case-control study. The PCR-RFLP method was used for genotyping. Data revealed that the GG genotype was related with a decreased risk of CP (GG vs TT: OR, 0.58, 95%CI, 0.37–0.92, P-value = 0.020; GG vs TG+TT: OR, 0.61, 95%CI, 0.39–0.94, P-value = 0.027). Besides, G allele was shown to decrease the risk of CP. In addition, the IL2 rs2069762 polymorphism was related with the severity of CP. To sum up, the IL2 rs2069762 polymorphism is related with a decreased risk and severity of CP in Chinese individuals.

Single nucleotide polymorphisms of whole genes and atrophic gastritis susceptibility:a systematic review and meta-analysis.

Atrophic gastritis (AG) is one of the important precancerous lesions of gastric cancer. Single nucleotide polymorphisms (SNPs) are closely related to AG susceptibility. However, the research conclusions on the predictive potential of SNPs are inconsistent. The study aims to retrospect the association between SNPs of whole genes and AG risk by meta-analysis. Up to April 29, 2020, a systematic literature search for the relationship of SNPs with AG susceptibility was performed utilizing PubMed, Web of Science and Chinese National Knowledge Infrastructure. The overall and stratified meta-analyses on extracted data were conducted by Stata11.2. 33 case-control studies were enrolled containing 9951 AG patients and 17,252 healthy controls, and 17 SNPs in 12 different genes were systematically reviewed. The results indicated that 12 genes could be categorized based on their functions, including immune response, cell proliferation and apoptosis, and DNA damage repair. For the SNPs in immune response-related genes, the C allele of TLR1 rs4833095 T/C increased AG risk to 1.21-fold and the recessive model of TLR4 rs11536878 in the TLR gene family decreased AG susceptibility to 0.48-fold. The variant alleles of IL-10 rs1800871 (OR=1.21) and IL-8 rs4073 (OR=1.22) in the IL gene family were positively associated with AG risk. PSCA rs2294008 enhanced AG risk in all genetic models. SNPs associated with AG susceptibility were mainly focused on immune response-related genes. These SNPs related to immune response could influence on AG risk and have potential to be AG predictive biomarkers. It is worth noting that the number of studies for each SNPs were insufficient due to the limited published researches and updated meta-analysis needs to be performed based on extensive relevant studies for more reliable results.

Allele frequency of promoter region -1082A>G interleukinl0 gene and risk of prostate tumors in Iraqi patients

Number of studies has demonstrated the relationship of interleukin 10 gene polymorphism with risk of prostate cancer. This research aimed to evaluate the effect of single nucleotide polymorphism in the promoter region rs1800896 of IL-10 -1082A >G on the incidence of benign prostate hyperplasia and prostate cancer in Iraqi patients. In this study, we studied IL-10 gene polymorphism in two groups of patients, thirty of whom have benign prostate hyperplasia and thirty have prostate cancer, as well as in thirty healthy subjects who were the control group. Relevant primers were used for the amplification by the polymerase chain reaction of the promoter region IL-10 rs1800896. Restriction fragment length polymorphism has been used to determine the frequencies of the alleles associated with each group of subjects studied. The amplified products of PCR were sequenced using the forward primer. The result of restriction fragment length polymorphism showed that AG, AA alleles were not found and GG allele was detected in all of the controls and patients, leading to a conclusion that AA, GG homozygotes and AG heterozygote alleles were not associated with both benign prostate hyperplasia and prostate cancer.

Single nucleotide variants in immune-response genes and the tumor microenvironment composition predict progression of mantle cell lymphoma

BackgroundThere is evidence to consider that the tumor microenvironment (TME) composition associates with antitumor immune response, and may predict the outcome of various non-Hodgkin lymphoma subtypes. However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients’ samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL.MethodsWe assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, IL17F) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models.ResultsHigh FOXP3/CD3 ratios (p = 0.001), high IL17A levels (p = 0.003) and low IL2 levels (p = 0.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (p = 0.02). In the SNV model, the CC haplotype of IL10 (p < 0.01), the GG genotype of IL2 rs2069762 (p = 0.02) and the AA+AG genotypes of TGFBR2 rs3087465 (p < 0.01) were independent predictors of outcome. Finally, the GG genotype of TGFB1 rs6957 associated with lower tumor TGFβ levels (p = 0.03) and less CD163+ macrophages (p = 0.01), but did not modulate patients’ survival.ConclusionsOur results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in IL10, TGFBR2 and IL2, may represent novel prognostic factors in this disease, following future validations.

Risk modelling further implicates the angiogenesis pathway in anterior cruciate ligament ruptures

ABSTRACT The aim of this study was to explore the interactions between the interleukins and the angiogenesis signalling pathway, following a pathway-based approach. Statistical modelling tools were used to develop a preliminary polygenic risk assessment model for anterior cruciate ligament (ACL) ruptures, incorporating the angiogenesis signalling genes (VEGFA and KDR) and interleukins (IL1B, IL6, IL6R) which also function to regulate angiogenesis. Multivariate logistic regression analysis was used to identify the most informative contributors to ACL rupture risk from a range of eleven potential intrinsic risk factors: age, sex, BMI and eight genetic polymorphisms within five genes, namely, IL1B rs16944 C/T, IL6 rs1800795 G/C, IL6R rs2228145 C/A, VEGFA rs699947 C/A, VEGFA rs1570360 G/A, VEGFA rs2010963 C/G, KDR rs2071559 A/G and KDR rs1870377 T/A. A total of 232 asymptomatic controls (CON) and 234 participants with surgically diagnosed ACL ruptures, of which 135 participants reported a non-contact mechanism of injury (NON subgroup), were previously genotyped for the selected polymorphisms. The polygenic risk model identified the VEGFA rs699947 CC genotype (p = 0.024, odds ratio (OR): 3.35, 95% confidence interval (CI): 1.17–9.62), VEGFA rs2010963 GC genotype (p = 0.049, OR: 2.43, 95% CI: 1.00–5.87), age (p = 0.011, OR: 0.97, 95% CI: 0.95–0.99) and BMI (p = 0.009, OR:1.09, 95% CI: 0.57–2.11) as the most significant predictors of ACL rupture risk from the data included. The results of this study highlight VEGFA, age and BMI as biologically significant components of this network requiring further investigation in the context of musculoskeletal soft tissue injury risk. Highlights The findings of this study highlight the VEGFA gene, age and BMI as biologically significant contributors to ACL rupture susceptibility. Upon further validation of these risk factors, they may be included in genetic risk assessment tools to design pre-habilitation strategies, prescribe appropriate treatment strategies after injury or to assess how an individual is likely to respond to load. Polygenic risk models aid in highlighting the components of the complex ECM remodelling pathway requiring further investigation, using a multidisciplinary approach. VEGFA is a key angiogenic protein contributing to ECM homeostasis and may therefore have potential therapeutic implications that need to be explored.

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.

Single nucleotide polymorphisms in interleukin-6 attenuates hepatocytes injury in hypoxia/re-oxygenation via STAT3 signal pathway mediated autophagy

Ischemia-reperfusion injury (IRI) is inevitable during liver surgery, and it is an important factor affecting the prognosis of patients. IL-6 rs1800796 single nucleotide polymorphisms (SNPs) can promote synthesis and secretion of IL-6 and protect hepatocytes from IRI. In this study, we investigated the mechanisms by which IL-6 alleviates hepatic IRI. We transfected lentivirus which carries IL-6 rs1800796 to L02 cells and constructed the cell line (L02-IL6) with a high expression of IL-6. The biological function of IL-6 SNPs was explored through a cell model of hypoxia-reoxygenation (H/R). Cell viability was evaluated by CCK8 and Real-Time Cell Analysis (RTCA), and found that the viability of the L02-IL6 cells was higher than that of the control group (P < 0.01). Flow cytometry assay showed that the rate of apoptosis was significantly decreased in L02-IL6 cells. Furthermore, in comparison with the control group, the level of cleaved-caspase3, which is an important marker of apoptosis, was dramatically decreased. These differences showed that the sequence variants at rs1800796 of the IL-6 gene could improve the resistance against H/R. Moreover, the levels of autophagy-related proteins, such as LC3 and Beclin-1, were upregulated in L02-IL6 group on H/R injury, which means IL-6 could alleviate apoptosis via activating the autophagy pathway. And we also found that the STAT3 signal pathway was activated. Next, we investigated whether the exogenous treatment with IL-6 affect hepatocytes and thus play a protective role. We pre-treated the L02 cells with recombinant human IL-6 for 12 h and then made H/R treatment. We found the treatment with 100 ng/ml IL-6 alleviated the damage of L02 cells and inhibited the apoptosis. And the further study revealed the pre-treatment with IL-6 activated the STAT3 signaling pathway in the L02 cells and then caused the activation of autophagy and apoptosis inhibition. IL-6 might play a critical role in alleviating hepatic IRI, through its modulation of the STAT3 signaling pathway, and activation of autophagy. Recombinant human IL-6 might be a potential therapeutic target in hepatic IRI.

Evaluation of IL1B rs1143634 and IL6 rs1800796 Polymorphisms with Autism Spectrum Disorder in the Turkish Children

ABSTRACT Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by genetic, environmental and immunological factors. It is known that neural development processes are affected by immune functions. The aim of this study is to evaluate the relationship between cytokines IL6 and IL1B gene polymorphisms in ASD. Methods DNA isolations were performed in 95 children diagnosed with ASD and 84 unrelated healthy children, single-nucleotide changes in IL6 (rs1800796) and IL1B (rs1143634) genes were determined by using Real-Time PCR (Real-Time Polymerase Chain Reaction) method. Results IL6 rs1800796 polymorphism presented an elevated risk for the development of ASD with CG genotype and dominant model (CG+GG vs. CC), CG+GG carriers (OR = 1.867, p = 0.057; OR = 1.847, p = 0.055, respectively). CT genotype in IL1B rs1143634 polymorphism associated with 2.33 times elevated risk of autism and showed a significant association compared to wild-type CC genotype (p = 0.02). IL1B rs1143634 polymorphism presented a significantly elevated risk for the development of ASD with recessive model (CC+CT vs.TT), TT genotype (OR = 8.145, p = 0.02). Conclusion This study concludes that rs1143634 is associated with the risk of ASD in Turkish children. Determining these polymorphisms in a larger sample group may contribute to understanding the etiology of ASD and developing new treatment protocols. Abbreviations ASD: Autism spectrum disorder; DNA: Deoxyribonucleic acid; IL6: Interleukin 6; IL1B: Interleukin 1 beta; Real-time PCR: Real-time polymerase chain reaction; JAK-STAT: The Janus kinase/signal transducers and activators of transcription; MAPK: The mitogen-activated protein kinase; 5ʹUTR: The 5′ untranslated region; IL1α: Interleukin 1 alpha; IL-1Ra: Interleukin 1 receptor antagonist; NF-κB: Nuclear factor-kappa B; DSM-V: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; M-CHAT: Modified Checklist for Autism in Toddlers; EDTA: Ethylenediaminetetraacetic acid; gDNA: Genomic DNA; HWE: Hardy–Weinberg equilibrium; ANK2: Ankyrin 2; NL3: Neuroligin-3; XRCC4: X-ray repair cross complementing 4

The Influence of Interleukin-2 Gene Polymorphisms on the Risk and Clinical Outcome of Non-Hodgkin Lymphoma.

Polymorphisms in the IL-2 gene are associated with various diseases and cancers including non-Hodgkin lymphoma (NHL). The aim of the study is to assess the impact of IL-2 genetic polymorphisms [- 330T/G (rs2069762) and + 114T/G (rs2069763)] on the susceptibility and prognosis of NHL. Sixty patients with NHL as well as 60 age and sex matched healthy control subjects are included in this study. IL-2 genotypes were determined by Polymerase Chain Reaction-Restriction Fragment length Polymorphism assay (PCR-RFLP). Our study revealed that both IL-2 rs2069762 and rs2069763 gene polymorphisms are associated with increased risk of developing NHL; OR = 3.609 (95% CI = 1.527-8.417) and 4.142 (95% CI = 1.637-10.538) respectively. Moreover, the simultaneous presence of both polymorphisms is associated with about 6 fold increased risk of developing NHL. Also, IL-2 rs2069762 and rs2069763 gene polymorphisms increase the risk of unfavorable prognosis with OR = 17.300 (95% CI = 3.392-87.725) and 10.424(95% CI = 1.870-58.413) respectively. These findings suggest that IL-2 (rs2069762) and (rs2069763) gene polymorphisms could be involved in the development of NHL.

Association between genetic polymorphism of IL-27 (rs153109) and toxoplasmosis in Iraqi women with recurrent abortion.

Single nucleotide polymorphisms (SNPs) are predictive markers for diseases, also cytokines are undergoing genetic controls and their genetic polymorphisms have a functional role in regulating the levels of cytokine gene expression. This study aims to reveal the association of toxoplasmosis with serum levels and SNP of IL-27 in aborted women. Total, 200 blood samples of patients and controls were collected from Al-Alawiya Maternity Teaching Hospital/Baghdad/Iraq from 2019–2020 for detecting the level of IL-27 by ELISA while the allelic discrimination method was used for SNP IL-27 (rs153109). The results indicated the IL-27 serum concentration elevated with significant differences in recurrent abortion with toxoplasmosis group compared to healthy women, pregnant women, and recurrent abortion. Also, recurrent abortion had significant differences compared to healthy women and pregnant women (P<0.05). Moreover, SNP results of IL-27 showed no significant association between patients and controls. Considering the distribution of serum levels for IL-27 by SNP, it was observed that IL-27 serum levels for TT, TC, and CC genotypes elevated in the patient group versus the control group. In addition, it was observed elevation serum level of IL-27 for the genotypes TT, TC, and CC in recurrent abortion with toxoplasmosis in contrast to healthy women, pregnant women, and recurrent abortion (P<0.05). Also, in recurrent abortion, the level of IL-27 for TC, and CC genotype showed significant differences comparing to healthy and pregnant women (P<0.05). In conclusion, the level of IL-27 in recurrent abortion women with toxoplasmosis was higher than the recurrent abortion women, which may be due to the inflammatory response to toxoplasmosis. SNP of IL-27 has not represented as a risk factor in recurrent abortion women with toxoplasmosis.

Association between Cytokine Gene Polymorphisms and Breast Cancer in Postmenopausal Women

The goal of this study was to investigate the association between the polymorphic loci of genes IL1B (rs16944), IL1RN (rs4251961), IL6 (rs1800795, rs1800796, rs1554606), IL8 (rs4073), IL10 (rs1800896), and TNFA (rs1800629) and breast cancer in women. The DNA samples of 521 women with breast cancer and 267 women without oncological pathology were studied. The study showed that age, concomitant chronic morbidity, and polymorphism of the IL6 gene are risk factors in postmenopausal women. Allele –572C (OR = 5.68; 95% CI = [2.70–11.97], pcor < 0.001), and haplotype rs1800796[C]–rs1800795[G]–rs1554606[G] (OR = 5.31, 95% CI = [1.87 – 15.10], pcor = 0.002) of the IL6 gene were associated with breast cancer. No association of loci in IL1B (rs16944), IL1RN (rs4251961), IL8 (rs4073), IL10 (rs1800896), or TNFA (rs1800629) was associated with the risk of breast cancer. The obtained data indicate that the –572C allele of the IL6 gene is associated with susceptibility in postmenopausal women to breast cancer. Our results can be useful for an understanding of the molecular mechanisms of breast cancer.