IL1B Rs16944 Research Articles

Polymorphism of IL-1β rs16944(T/C) Associated with Serum Levels of IL-1β and Subsequent Stimulation of Extracellular Matrix Degradation Affects Intervertebral Disk Degeneration Susceptibility.

PurposeTo investigate the association of polymorphism of IL-1β rs16944(T/C) with intervertebral disk degeneration (IDD), explore the possible mechanism and evaluate the predictive value of IL-1β for IDD.Patients and MethodsA total of 196 consecutive patients with IDD were recruited, and 196 healthy controls were matched to these patients based on sex and age (±3 years). The polymorphisms of IL-1β rs16944(T/C), rs1143623(G/C), rs10490571(T/C) and rs2853550(A/G) were determined, and serum IL-1β, MMP-1, MMP-3, MMP-9 and a disintegrin-like and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) levels were measured. Univariate analysis was performed with Student t-test or one-way ANOVA followed by post hoc and Chi-square test. Variables with two-sided P<0.10 were included in multivariate analysis, which employed a backward stepwise logistic regression model. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value.ResultsMultivariate analysis showed that the polymorphism of IL-1β rs16944(T/C) was independently associated with IDD. The risk for IDD was significantly increased in TT and TC genotype compared with CC genotype, and the OR of TT genotype was higher than that of TC genotype. ANOVA analysis showed that serum concentration of IL-1β was highest in IL-1β rs16944 TT genotype, intermediate in TC genotype, and lowest in CC genotype. Similarly, serum concentrations of MMP-3 and ADAMTS-4 demonstrated the same tendency of TT > TC > CC genotype. Serum concentrations of MMP-1 and MMP-9 were higher in TT genotype than in TC and CC genotype. The area under curve (AUC) of IL-1β levels in predicting IDD was 0.788 (SE: 0.023, P=0.001, 95% CI: 0.742–0.834), and the predictive value was modest with a sensitivity of 77.0% and a specificity of 75%.ConclusionPolymorphism of IL-1β rs16944(T/C) affected IDD susceptibility through upregulation of serum levels of IL-1β and subsequent stimulation of ECM degradation. IL-1β levels could be applied in predicting IDD.

Association of interleukin-12B rs6887695 with susceptibility to allergic rhinitis.

Interleukin-12 (IL-12) is a heterodimeric cytokine encoded by two separate genes, IL12A and IL12B, which may play a regulatory role in allergen-induced inflammation through CD4+ T-cell subsets polarization. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) in the IL12B gene with susceptibility to allergic rhinitis (AR). We performed a case-control study including 130 AR patients and 130 healthy controls to evaluate the possible association between IL12B gene SNPs (rs3212227, rs6887695) and the risk of AR using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our results showed no significant association between IL12B rs3212227 A > C polymorphism with AR. In contrast, the GC genotype of rs6887695 G > C was associated with susceptibility to AR in comparison with the GG genotype (p = 0.049, OR = 1.684, 95% CI: 1.002-2.83). We also observed a statistically significant difference in the additive model (GC versus GG + CC, p = 0.03, OR = 1.705, 95% CI: 1.040-2.794) for SNPs rs6887695. Furthermore, haplotypes analysis demonstrated that C-C haplotype was associated with an increased risk of AR (p = 0.01, OR = 1.845, 95% CI: 1.114-3.057). Our findings suggest that IL12B rs6887695 polymorphism may be a potential biomarker for susceptibility to AR in an Iranian population.

Relationships between IL-1β, TNF-α genetic polymorphisms and HBV infection: A meta-analytical study.

IL-1β and TNF-α have been demonstrated as pro-inflammatory cytokines to participate in the innate immune response and suppression of HBV infection. However, the exact relationship between IL-1β, TNF-α gene polymorphisms and HBV infection remains unknown. Our study aims to assess the associations between IL-1β, TNF-α gene polymorphisms and HBV infection. A systematic literature search of PubMed and Embase databases was conducted through February 2020, and studies that were included in the present meta-analysis should fulfil the following conditions: (1) case-control studies focusing on the associations between IL-1β, TNF-α polymorphisms and HBV infection; (2) patients in the case group should be tested positive for the HBsAg and/or HBV-DNA without liver cirrhosis or hepatocellular carcinoma; (3) the control group including healthy population or HBV spontaneous clearance population; (4) odds ratios (ORs) and their 95% confidence intervals (CIs) could be calculated based on the allele and genotype frequencies provided in articles. The quality of included studies was assessed according to the Newcastle-Ottawa scale (NOS) assessment system. Pooled ORs and 95% CIs were used to analyze the strength of associations. Subgroup analysis was performed according to ethnicity and control type. In the present meta-analysis, 49 articles including 10,218 cases and 9,557 controls were enrolled and seven polymorphisms (IL-1β rs16944, rs1143634, TNF-α rs1799724, rs1799964, rs1800629, rs1800630, rs361525) were studied. In overall meta-analysis, significant associations were found in IL-1β rs1143634, TNF-α rs1799724 and TNF-α rs1799964. For subgroup analysis under ethnicity, TNF-α rs1799724 and rs1800630 were markedly related to HBV infection in both Asian and Caucasian populations. In terms of control type subgroup, TNF-α rs1799724, rs1799964, rs1800630 were significantly associated with HBV persistence in HBV spontaneous clearance group. In the present study, we identified that three polymorphisms (IL-1β rs1143634, TNF-α rs1799724, rs1799964) might serve as potential genetic biomarkers in HBV infection.

Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis.

PurposeOver a third of patients with Acanthamoeba keratitis (AK) experience severe inflammatory complications (SICs). This study aimed to determine if some contact lens (CL) wearers with AK were predisposed to SICs due to variations in key immune genes.MethodsCL wearers with AK who attended Moorfields Eye Hospital were recruited prospectively between April 2013 and October 2014. SICs were defined as scleritis and/or stromal ring infiltrate. Genomic DNA was processed with an Illumina Low Input Custom Amplicon assay of 58 single nucleotide polymorphism (SNP) targets across 18 genes and tested for association in PLINK.ResultsGenomic DNA was obtained and analyzed for 105 cases of AK, 40 (38%) of whom experienced SICs. SNPs in the CXCL8 gene encoding IL-8 was significantly associated with protection from SICs (chr4: rs1126647, odds ratio [OR] = 0.3, P = 0.005, rs2227543, OR = 0.4, P = 0.007, and rs2227307, OR = 0.4, P = 0.02) after adjusting for age, sex, steroids prediagnosis, and herpes simplex keratitis (HSK) misdiagnosis. Two TLR-4 SNPs were associated with increased risk of SICs (chr9: rs4986791 and rs4986790, both OR = 6.9, P = 0.01). Th-17 associated SNPs (chr1: IL-23R rs11209026, chr2: IL-1β rs16944, and chr12: IL-22 rs1179251) were also associated with SICs.ConclusionsThe current study identifies biologically relevant genetic variants in patients with AK with SICs; IL-8 is associated with a strong neutrophil response in the cornea in AK, TLR-4 is important in early AK disease, and Th-17 genes are associated with adaptive immune responses to AK in animal models. Genetic screening of patients with AK to predict severity is viable and this would be expected to assist disease management.

Association between Interleukin-1β Polymorphism at Rs16944 and Glucose Metabolism: A Cohort Study

ABSTRACT Background This study explored the correlation between the interleukin-1β gene rs16944 polymorphism and diabetes through epidemiological and follow-up investigations. Methods The study was conducted on 600 subjects with normal glucose metabolism recruited from participants of the Risk Evaluation of cAncers in Chinese type 2 diabeTic Individuals: A lONgitudinal (REACTION) study in Luzhou, China in 2011. All subjects received a unified standardized questionnaire, physical examination, laboratory examination, and follow-up in 2016. Subjects were divided into normal glucose metabolism (NC), pre-diabetes (PDM), and type 2 diabetes mellitus (T2DM) groups according to their glucose metabolism after follow-up. The IL-1β gene rs16944 polymorphism was analyzed using the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique. Results After follow-up, 386, 156, and 58 cases were observed in the NC, PDM, and T2DM groups, respectively. Serum IL-1β levels were compared to baselines at follow-up in the 3 groups; the difference in the T2DM group was statistically significant. The frequency distributions of the IL-1β gene rs16944 genotypes, i.e., CC, CT, and TT, were significantly different in the 3 groups, and the distributions in the T2DM and NC groups were significantly different. The frequency distributions of the C and T alleles of IL-1β rs16944 were not significantly different. Logistic regression analysis identified the CC+CT genotype as an independent risk factor for the development of diabetes in patients with normal glucose metabolism (OR = 2.457, 95% CI: 1.238–4.877). Conclusions The IL-1β gene rs16944 C/T polymorphism may cause genetic susceptibility to T2DM in the Luzhou population. The CC+CT genotypes may increase T2DM risk.

The association between Interleukin-1β gene polymorphisms and the risk of breast cancer: a systematic review and meta-analysis

IntroductionIt is reported that there is a close association between interleukin-1β (IL-1β) gene polymorphisms and breast cancer risk. However, the results remain controversial.Material and methodsEligible published articles were searched in PubMed, Embase, and Web of Science databases up to June 2018. Odds ratios with 95% confidence intervals were used to identify potential links between IL-1β genetic polymorphisms and the risk of breast cancer.ResultsFrom our results, we found that three common polymorphisms in IL-1β (rs16944, rs1143634, rs1143627) had no significant associations with breast cancer risk in all genetic models. Based on the analysis from ethnic subgroups, there was a higher risk of breast cancer for rs16944 polymorphism in the recessive model and heterozygous model among Asians (TT vs. CC+CT: 1.229, 95% CI: 1.063–1.422, p = 0.005; TT vs. CT: 1.211, 95% CI: 1.057–1.388, p = 0.006). For the rs1143627 polymorphism, a significantly decreased breast cancer risk was observed in the dominant model only in Asians (CT+TT vs. CC: OR = 0.944, 95% CI: 0.897–0.994, p = 0.027). After stratifying patients according to the menopausal state, we found that polymorphism of rs1143627 correlated with reduced breast cancer risk among post-menopausal women in three genotype models: allele, recessive model and homozygous model (T vs C: 0.859, 95% CI: 0.753–0.98, p = 0.024; TT vs. CC+CT: 0.727, 95% CI: 0.576–0.918, p = 0.007; TT vs. CC: 0.743, 95% CI: 0.626–0.882, p = 0.001). As for other analyses with reference to source of controls and genotyping methods, no significant association between IL-1β polymorphism and breast cancer risk was demonstrated.ConclusionsThe rs16944 and rs1143627 polymorphisms are significantly associated with the risk of breast cancer only in Asian people and in post-menopausal women respectively.

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.

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.

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

CARD8 and IL1B Polymorphisms Influence MRI Brain Patterns in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia.

Inflammation and oxidative stress are recognized as important contributors of brain injury in newborns due to a perinatal hypoxic-ischemic (HI) insult. Genetic variability in these pathways could influence the response to HI and the outcome of brain injury. The aim of our study was to evaluate the impact of common single-nucleotide polymorphisms in the genes involved in inflammation and response to oxidative stress on brain injury in newborns after perinatal HI insult based on the severity and pattern of magnetic resonance imaging (MRI) findings. The DNA of 44 subjects was isolated from buccal swabs. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1B rs16944, IL1B rs1143623, IL1B rs1071676, TNF rs1800629, CAT rs1001179, SOD2 rs4880, and GPX1 rs1050450. Polymorphism in CARD8 was found to be protective against HI brain injury detected by MRI overall findings. Polymorphisms in IL1B were associated with posterior limb of internal capsule, basal ganglia, and white matter brain patterns determined by MRI. Our results suggest a possible association between genetic variability in inflammation- and antioxidant-related pathways and the severity of brain injury after HI insult in newborns.

FGB, TNFα, IL-1β, LPL, ITGB3, and TGFB1 genes polymorphism in patients with recurrent myocardial infarction

The aim . To evaluate the association of fibrinogen ( FGB ), tumor necrosis factor α ( TNF α), interleukin 1β ( IL-1 β), lipoprotein lipase ( LPL ), platelet glycoprotein ( ITGB3 ), and transforming growth factor β ( TGFB1 ) genes with the incidence of recurrent myocardial infarction (MI) in patients living in the middle Volga region. Materials and methods . The study included 104 people with recurrent MI compared to 280 people who had just one episode of MI. TNFα (rs1800629), IL1B (rs16944), TGFB1b (rs1800469), FGB (rs1800788), ITGB3 (rs5918) and LPL (rs328) gene polymorphism was determined in all patients using competing TaqMan probes. Association estimation was performed with multivariate logistic regression analysis. Results . Patients with recurrent MI much more often had TNFα , IL1B , TGFB1b , FGB , ITGB3 and LPL allele and genotype polymorphism. Moreover the risk of MI increased significantly in a case of combination of FGB (alleles and genotypes) and TNF α (alleles and genotypes) gene polymorphisms (OR = 4.04, 95% CI = (1.895–8.615), p = 0.0001). Conclusion . Thus, FGB , LPL , TNF α, TGFB1b and ITGB3 gene polymorphism are associated with more severe coronary heart disease and may be a risk factor of recurrent MI development. The dominant total contribution of the FGB (rs1800788) and TNF α (rs1800629) polymorphic genes to the development of recurrent MI in the population of the middle Volga region was revealed.

IL-17A polymorphism (rs2275913) and levels are associated with preeclampsia pathogenesis in Chinese patients

BackgroundPreeclampsia (PE) is a pregnancy-related condition that affects both the infant and the mother. Although the role of various inflammatory molecules in PE has been demonstrated, the importance of pro-inflammatory molecules such as IL-17A, IL-23 is not well understood. In the present investigation, a potential association of common genetic variants in the IL-17A and IL-23A genes with PE was investigated.Methods115 PE clinically diagnosed patients who registered to the International Peace Maternity and Child Health Hospital were enrolled in this research. One hundred two pregnant women and 147 healthy Chinese women were also included. ELISA was used to measure IL-17A and IL-23 serum levels in all enrolled subjects. Common genetic polymorphisms in IL-17A (rs 2,275,913, rs1974226, and rs1974226), IL-23A (rs11171806), and IL-12B (rs3212227) were genotyped using the PCR-RFLP or TaqMan probe-based method.ResultsElevated serum IL-17A levels were found in PE patients compared to pregnant (P < 0.0001) and healthy women (P < 0.0001). However, IL-23 levels were comparable across various clinical groups. In addition, heterozygous (GA) and minor allele (A) for IL-17A (rs2275913) and IL-23A (rs11171806) were more prevalent in PE patients compared to pregnant women indicating an important role in the predisposition to PE growth. Interestingly, IL-17A (r 2,275,913) mutants were associated with elevated IL-17A levels relative to wild type (GG).ConclusionsIL-17A (rs2275913) variants are associated with higher serum levels of cytokine, and predisposed PE development.

The Polymorphisms of Interleukin-12B Gene and Susceptibility to Inflammatory Bowel Diseases: A Meta-analysis and Trial Sequential Analysis

ABSTRACT Objective: Inflammatory bowel disease (IBD) is a heterogeneous complex disease referring to two chronic disorders: Crohn’s disease (CD) and ulcerative colitis (UC). To clarify the relationship between IL-12B gene polymorphisms and susceptibility to CD and UC, a meta-analysis was conducted. Methods: A comprehensive search of the PubMed, Web of Science, Embase and Cochrane databases was conducted up to Oct 2019. Studies evaluating the relationship between risk of IBD and variants of IL-12B (rs6887695, rs3212227 and rs10045431) were included. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Trial sequential analysis (TSA) was implemented to estimate the required information size (RIS) and evaluate the credibility of the meta-analysis results. Results: Seventeen studies containing 9827 patients with CD, 7583 patients with UC and 16044 controls were included. The results showed significant association between rs6887695 polymorphism and susceptibility to CD (allele model: OR = 1.17, 95% CI: 1.12–1.22) and UC (allele model: OR = 1.16, 95% CI: 1.09–1.23), and “C” allele carriers had a higher risk, with TSA conclusive. For rs10045431, no significant association with CD susceptibility was identified, while a significantly increased risk in UC was found (allele mode: OR = 1.16, 95% CI: 1.07–1.25), both results were conclusive according to TSA. No significant association between rs3212227 and CD or UC susceptibility was found, and TSA research warranted further investigation to certify the results. No significant heterogeneity was found. Conclusion: IL-12B rs6887695 polymorphism was associated with increased risk of CD and UC, while IL-12B rs10045431 polymorphism might only be correlated with the risk of UC. Abbreviations: IBD: inflammatory bowel disease; CD: Crohn’s disease; UC: ulcerative colitis; IL-12B: interleukin-12B; OR: odds ratio; CI: confidence interval; TSA: trial sequential analysis; RIS: required information size; DCs: dendritic cells; NK: nature killer; APCs: antigen-presenting cells; TNF: tumor necrosis factor; SNP: single nucleotide polymorphisms; HWE: Hardy–Weinberg equilibrium; NOS: Newcastle–Ottawa scale; RRR: relative risk reduction

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.

Assessment of Interleukin-12 Gene Polymorphism in Vitiligo Patients

Vitiligo is an obtained pigmentary turmoil of the skin and mucous films. Interleukin-12 has a positive synergistic proliferative impact on pre-initiated NK and T cells, improves freely and additionally synergistically the cytolytic capacity of both NK and CD8+ T cells by upregulation of qualities that encode cytotoxic cell granule-related proteins. The point of the work is to uncover the relationship between IL-12 quality polymorphism and vitiligo pathogenesis among contemplated gathering of Egyptian populace. This case-control study included 50 patients experiencing vitiligo (Group A) and 50 obviously solid people of coordinated age and sex as a benchmark (Group B). All patients were exposed to the followings: Full history taking, Clinical assessment, and Laboratory examinations for the genotypes of interleukin-12 (1188 A/C) SNP. Results and Conclusion: The IL12B rs3212227 CC genotype and C allele indicated fundamentally lower recurrence in situations when contrasted with control bunches with defensive impact to create vitiligo cases. Negative family ancestry, non-smokers and CC genotype were viewed as defensive indicators against vitiligo powerlessness. More seasoned period of beginning, more limited illness term, CA and CC genotypes were viewed as free indicators of less extreme vitiligo patients. By and by, bigger examinations are as yet expected to affirm our discoveries and to research the function of - 12 hereditary polymorphism in sickness seriousness.

Gene Polymorphisms Increasing the Risk of Intracranial Aneurysms: Interleukin-1β -511C>T (Part I).

Introduction:Intracranial aneurysms (IAs) are devastating cerebrovascular diseases with multifactorial etiology. The role of inflammation is indisputable, and interleukins are pivotal in supporting local inflammatory pathways and endothelial dysfunction at the aneurysm wall. In the light of insufficient evidence reported in the literature, this meta-analysis was aimed to investigate the genetic linkage between IL-1β (rs16944) -511C>T polymorphisms and IAs susceptibility.Methods:A comprehensive online literature review was completed using the PubMed/Medline and Web of Science databases in accordance with the PRISMA guidelines. “Interleukin-1β,” “IL-1β,” “polymorphism,” “intracranial aneurysm,” and “subarachnoid hemorrhage” were the main keywords. Only human case-control studies, published from 2005 to 2021, written in English or translated, were screened. In the statistical analysis, we applied the fixed-and random-effect models, according to the level of heterogeneity, to assess the odds ratios (ORs) and 95% confidence intervals (CIs). RevMan 5.0 software was used for the statistics.Results:Only 4 studies were eligible, with a total of 2070 patients, 1050 of which were assigned to the study group. Combined results showed a statistically significant association between the risk of IAs and -511CC (OR=0.79, 95% CI [0.65-0.95], p=0.01), and CT (OR=0.69, 95% CI [0.58-0.82], p<0.0001; OR=0.71, 95% CI [0.55-0.93], p=0.01) allele variations, both in the fixed-and random-models. No correlation was identified for the -511TT genotype (p=0.42; p=0.78). All the texts showed a low level of publication bias.Conclusion:The present meta-analysis proved a potential role of IL-1P -511CC/CT genotypes in the pathogenesis of IAs. Additional studies are imperative to explain the underlying neuroimmune mechanisms, also allowing tailoring the potential inflammatory-target therapies for IAs. (www.actabiomedica.it)

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

Association of Polymorphisms in Inflammatory Cytokines Encoding Genes With Anti-N-methyl-D-Aspartate Receptor Encephalitis in the Southern Han Chinese

Background: Single nucleotide polymorphisms (SNPs) that occur within genes encoding inflammatory cytokines can result in quantitative or qualitative changes in their expression or functionality, potentially leading to the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. This study sought to evaluate the relationship between SNPs in inflammatory cytokines genes and the incidence of anti-NMDAR encephalitis in the Southern Han Chinese.Methods: In total, we enrolled 107 patients with anti-NMDAR encephalitis as well as 202 inpatient controls who had no first-degree relative with autoimmune diseases. Genotyping determination of all 309 patients was conducted for the IL-1β rs16944, IL-4 rs2243250, IL-4 rs2070874, IL-6 rs1800796, IL-10 rs1800872, and IL-17 rs2275913 gene SNPs.Results: We observed statistically significant differences in the frequencies of G allele in IL-1β rs16944 between anti-NMDAR encephalitis and controls (p = 0.017). Also, IL-1β, IL-4, IL-6, IL-10, and IL-17 SNPs were not associated with the disease (p > 0.05).Conclusions: We found that patients with anti-NMDAR encephalitis exhibit a distinct immunological profile, and we found that the decreased frequency of G allele in IL-1β rs16944 showed a protective role for anti-NMDAR encephalitis in the Southern Han Chinese.

Detection of association of IL1β, IL4R, and IL6 gene polymorphisms with cervical cancer in the Bangladeshi women by tetra-primer ARMS-PCR method

BackgroundCervical cancer (CC) is the main cause of cancer-related deaths among women in developing countries. It is the second leading female malignancy in Bangladesh in terms of incidence and mortality. Our present study aimed to investigate the association of IL1β (rs16944), IL4R (rs1801275), and IL6 (rs1800797) gene polymorphisms with the susceptibility of cervical cancer. Materials and MethodsThis case-control study was conducted on 252 cervical cancer patients and 228 healthy volunteers, using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). ResultsIn the case of rs16944 polymorphism, GG genotype (OR = 2.10, 95%CI = 1.24–3.56), dominant model (OR = 1.71, 95% CI = 1.11–2.63), recessive model (OR = 1.54, 95% CI = 1.01–2.35), and G allele (OR = 1.30, 95% CI = 1.005–1.68) were significantly associated with increased cervical cancer risk. Among these, GG genotype and dominant model remained significant after the Bonferroni correction (p < 0.017). For rs1801275 polymorphism, GG genotype (OR = 2.66, 95% CI = 1.49–4.75), dominant model (OR = 1.49, 95% CI = 1.04–2.14), recessive model (OR = 2.45, 95% CI = 1.40–4.27), and G allele (OR = 1.59, 95% CI = 1.21–2.10) significantly elevated the risk of cervical cancer but significance did not exist for dominant model after the Bonferroni correction. rs1800797 variant showed significantly increased risk in all genetic models including, AG genotype (OR = 8.13, 95% CI = 5.27–12.55), AA genotype (OR = 9.86, 95% CI = 2.76–35.21), dominant model (OR = 8.25, 95% CI = 5.40–12.60), recessive model (OR = 4.41, 95% CI = 1.25–15.56), and A allele (OR = 4.99, 95% CI = 3.49–7.13) and the significances were consistent with the Bonferroni correction except recessive model. Haplotyping analysis indicates that GAA (p = 5.15x10−5) and GAG haplotypes (p = 4.72x10−9) significantly decreased the risk of CC, whereas AAA (p = 3.89x10-9), AAG (p = 0.0003), AGA (p = 3.98x10-5) and AGG haplotypes (p = 0.002) significantly increased the risk of CC. The IL1β mRNA level was up-regulated, which was associated with poor prognosis in silico. ConclusionOur results conclude that rs16944 (IL1β), rs1801275 (IL4R), and rs1800797 (IL6) polymorphisms are associated with cervical cancer in Bangladeshi women.

Genetic Variability in Antioxidative and Inflammatory Pathways Modifies the Risk for PCOS and Influences Metabolic Profile of the Syndrome.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder of multifactorial etiopathology likely to involve the interactions between genetics and lifestyle. Chronic inflammation and oxidative stress (OS) may participate in the pathophysiology of the syndrome. The question of the extent to which OS and inflammation are causally related to the development of the syndrome and metabolic complications remains unanswered. By our knowledge, the role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as an important trigger of inflammatory pathways and NLRP3 and CARD8 polymorphisms has never been addressed in PCOS yet. We conducted a case-control study conducting of total 169 Slovenian PCOS patients and 83 healthy blood donors. They were genotyped for polymorphisms in antioxidative (SOD2 rs4880, CAT rs1001179, PON1 rs854560, and rs662) and inflammatory pathways genes (NLRP3 rs35829419, CARD8 rs2043211, TNF rs1800629, IL1B rs1143623, and rs16944, IL6 rs1800795) using competitive allele-specific polymerase chain reaction (PCR). Logistic regression and the Mann–Whitney test were used in the statistical analysis. SOD2 rs4880, CARD8 rs2043211, and IL1B rs16944 were associated with the risk of developing PCOS. Furthermore, the interactions between CARD8 rs2043211 and IL6 rs1800795 and between IL1B rs1143623 and IL6 rs1800795 also significantly affected the risk for PCOS. With regard to glucose homeostasis, CAT rs1001179, SOD2 rs4880, PON1 rs854560, NLRP3 rs35829419, and TNF rs1800629 were significantly associated with response to the glycemic load. Our data indicate that the genetic variability in the antioxidative and inflammatory pathways influences the development of PCOS and glucose homeostasis in PCOS patients.