IL1B Rs16944 Research Articles

Interleukin-1 Beta rs16944 and rs1143634 and Interleukin-6 Receptor rs12083537 Single Nucleotide Polymorphisms as Potential Predictors of COVID-19 Severity.

Host genetic variation has been recognized as a key predictor of diverse clinical sequelae among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. Insights into the link between the Interleukin-6 receptor (IL-6R) and Interleukin-1 beta (IL-1β) genetic variation and severe coronavirus disease 2019 (COVID-19) are crucial for developing new predictors and therapeutic targets. We aimed to investigate the association of IL-6R rs12083537, IL-1β rs16944, and IL-1β rs1143634 SNPs with the severity of COVID-19. Our study was conducted on 300 COVID-19-negative individuals (control group) and 299 COVID-19-positive cases, classified into mild, moderate, and severe subgroups. Analyses of IL-1β (rs16944, rs1143634) and IL-6R (rs12083537) SNPs' genotypes were performed using qPCR genotyping assays. The IL-1β (rs16944) CC genotype and IL-6R (rs12083537) GG genotype were substantially related to COVID-19 severity, which was also associated with comorbidities and some laboratory parameters (p < 0.001). The IL-1β (rs1143634) TT genotype was found to be protective. Likewise, the IL-1β (rs16944) CC genotype was associated with increased mortality. IL-1β rs16944 and IL-6R rs12083537 SNPs are promising potential predictors of SARS-CoV-2 disease severity. Meanwhile, the rs1143634 SNP T allele was protective against severity and mortality risk.

Cytokine gene polymorphisms and suicide risk in an Indian ancestral population: A case-control study

Background India currently accounts for a majority of global suicide deaths. Research in European ancestry has established that suicide mortality has a significant genetic component, and suggests that inflammation may play a crucial role in the pathophysiology of suicide. Inflammation is also highly relevant in regions of increased pollution exposure, such as the megacities of India. To address the existing gaps in genetic research on suicide and possible association with inflammatory biomarkers, we examined genetic polymorphism and clinical risk phenotypes in a population-based suicide-death cohort, India. Material and methods Genotyping of IL-1β(rs16944) & (rs1143627), IL-4(rs2070874), IL-6(rs1800795) and IL-10(rs1800896) was done in 234 post-mortem suicide-death cases and 256 post-mortem controls (N = 490) using PCR RFLP method. Results Our analyses identified three significant (p < 0.001) associations of cytokine variants with suicide death, including IL-1β(rs16944), OR = 0.627; IL-4(rs2070874), OR = 0.524; and IL-6(rs1800795), OR = 2.509. Cases were more likely female and were more likely to have a history of psychiatric illness, though rate of psychiatric illness was low in suicide cases(9%). Conclusion Our genetic results are generally consistent with previous research on risk for depression and suicidal behaviour, and both genetic and phenotypic results provide new insights into risk factors that may contribute to suicide in India.

Inflammatory and genomic interactions within keratoconus susceptible patients: a nationwide registered case–control study

PurposeThis study aimed to investigate the association between variants in the interleukin (IL)-1 gene cluster and susceptibility to keratoconus (KC) in an Iranian population.MethodsIn the case group, there were 188 KC patients diagnosed by clinical findings and corneal tomography. The control group included all 205 healthy controls with no personal or family history of eye-related, metabolic, or immune system-related disease. Using the standard salting out extraction procedure, genomic DNA was isolated from peripheral blood leukocytes. The genotypes were determined by applying agarose gel electrophoresis for the IL-1RN 86 bp VNTR and polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) for rs16944 and rs1143634.ResultsThe results showed a significant association between the IL-1β rs1143634 (rs1143634 T allele, P = 0.008) and IL-1RN 86 bp VNTR polymorphisms (LL and LS genotype, P = 0.048 and 0.012 respectively) and susceptibility to KC in the Iranian population. The genotype distributions of rs1143634 (P = 0.004) and rs2234663 (P = 0.042) significantly differed between case and control groups, with certain genotypes demonstrating a protective effect against KC. Logistic regression analysis revealed a protective effect of the IL-1RN L allele [odds ratio (OR) = 0.367, 95% confidence interval (CI): 0.240–0.562; P = 0.000] and certain haplotypes (OR = 0.628, 95% CI: 0.447–0.884; P = 0.007) against KC. However, no significant association was found for the IL-1β rs16944 polymorphism.ConclusionThis study provides evidence for an association between variants in the IL-1 gene cluster and susceptibility to KC in an Iranian population. Further research on larger and more diverse populations is warranted to validate these findings and explore the underlying mechanisms involved.

Effect of genetic polymorphisms of interleukin-1 beta on the microscopic portal vein invasion and prognosis of hepatocellular carcinoma.

Several studies have demonstrated a relationship between genetic polymorphisms of interleukin-1 beta (IL-1β) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL-1β single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma. We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence-free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells. A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p = .03 and .04). In multivariate analysis, A/A genotype, alpha-fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p = .01, .01, and <.01). A/A genotype, Child-Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p = .02, <.01, and <.01). Our results indicate that the IL-1β rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC.

Associations between IL-1β, IL-6, and TNFα polymorphisms and longitudinal trajectories of cognitive function in non-demented older adults

Inflammation is implicated in Alzheimer's disease (AD), and specific single nucleotide polymorphisms (SNPs) in inflammatory cytokine genes are associated with increased AD risk. Whether the same polymorphisms also predict domain-specific cognitive change in cognitively healthy older adults is unclear. Specific SNPs in three cytokine genes, IL-1β (rs16944), IL-6 (rs1800795), and TNFα (rs1800629) were assessed for association with longitudinal trajectories spanning up to 16 years of global cognitive function, episodic memory, attention and working memory, and executive function in a sample of 324 non-demented older adults. Only rs1800629 (TNFα) was associated with significant change in global cognitive function over time [γ = 5.22; 95% CI: 0.61, 9.83; p = 0.027]. Despite an association with AD risk, rs16944 and rs1800795 may not predict cognitive decline in cognitively healthy older adults. The presence of an A at rs1800629 (TNFα) may have broad, protective effects on cognitive function, over time. More validation studies are needed to determine whether specific cytokine SNPs are associated with respective serum levels to further understanding of AD biomarkers that may also serve as markers of cognitive decline.

Association of single nucleotide polymorphisms (SNPs) in inflammatory pathways with breast cancer (BC) risk: A multi-ethnic scoping review.

1617 Background: Breast cancer is the most prevalent cancer affecting women of every ethnic group in the United States. This is a scoping review assessing SNPs in inflammatory pathways posited to modify BC risk by ethnicity. Methods: We followed PRISMA guidelines for scoping reviews. PubMed, Medline, and OVID databases were interrogated for publications between 1/2000-12/2023 using search terms “breast cancer” AND [BMI OR “body mass index” OR elevated BMI OR obesity] AND [SNP OR “single nucleotide polymorphism” OR polymorphism OR mutation] AND [inflammation OR cytokines OR IL-1 OR IL-2 OR IL-4 OR IL-6 OR IL-8 OR IL-10 OR IL-12 OR TNF-A or TGFB OR CRP] AND [Asian, Black or Hispanic]. A single reviewer assessed 72 unique publications and determined that 42 met inclusion criteria. Two reviewers extracted the following data: demographics, SNP, number of cases and controls by ethnicity. Disagreements were resolved by consensus with a third reviewer. Results: Data were extractable from 42 studies, all case controls. In analyses stratified by ethnicity, we detected effects of SNPs on BC risk (Table). IL-1β rs1143634 and IL-10 (1082 A/G) had a significantly increased BC risk in Asian populations but insignificant in white populations. There were minimal publications for Black and Hispanic populations. Conclusions: The association of inflammatory SNPs and BC risk is complex and can be both protective and predisposing to BC, with ethnicity modifying SNP risk. Future research can be directed at assessment of SNPs and BC risk in diverse populations. [Table: see text]

Predicting the risk of developing vibration disease and vegetative-sensory polyneuropathy under vibration exposure using analysis of candidate gene polymorphism

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

Прогнозирование риска развития вибрационной болезни и вегетативно-сенсорной полинейропатии при вибрационном воздействии с исполь-зованием анализа полиморфизма кандидатных генов

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

Polymorphism of Genes Encoding Inflammatory Interleukins and the Risk of Anterior Cruciate Ligament Injury: A Systematic Review and Meta-Analysis.

Sport injuries, including the anterior crucial ligament rupture (ACLR) seem to be related to complex genetic backgrounds, including the genes responsible for inflammatory response. This review and meta-analysis investigated the contribution of the polymorphisms of genes encoding inflammatory cytokines and their receptors to the risk of ACLR. The scientific databases Science Direct, EBSCO host, Scopus, PubMed, and Google Scholar were screened (completed on 14 June 2023) according to the established inclusion/exclusion criteria (only fully accessible, original, human case-control studies written in English concerning the effect of interleukin genes' polymorphisms on the occurrence of ACL injury were included) and statistical meta-analysis using R version 4.0.3 was performed. The PRISMA methodology was used to review articles. The review protocol was registered under the number CRD42024514316 in the Prospero database. Eighty-nine studies were identified and narrowed down to three original case-control studies used for the meta-analysis. The studies analyzed Polish, South African, and Swedish cohorts, altogether 1282 participants. The candidate polymorphisms indicated in the studies involved IL6 rs1800795, IL6R rs2228145 and IL1B rs16944. The systematic review showed the relationships between IL6 rs1800795 polymorphism and ACLR in the Polish subpopulation, and IL6R rs2228145 and IL1B rs16944 in the South African subpopulations. The meta-analysis revealed that the IL6 rs1800795 CG genotype was over-represented (OR = 1.30, 95% CI 1.02-1.66), while the CC genotype was under-represented (OR = 0.75, 95% CI 0.54-1.03) in ACLR subjects, but no significant impact of IL6R rs2228145 was shown. Additionally, a tendency of the IL1B rs16944 CT genotype to be protective (OR 0.89, 95% CI 0.70-1.14), while the TT to be a risk genotype (OR 1.19, 95% CI 0.84-1.68) was observed. Thus, the relationship between the interleukin receptor IL6R rs2228145 and ACLR risk was not confirmed. However, the impact of genes coding pleiotropic IL6 rs1800795 on the incidences of ACLR was clear and the effect of pro-inflammatory IL1B rs16944 was possible.

IL-10 and IL-1β Serum Levels, Genetic Variants, and Metabolic Syndrome: Insights into Older Adults' Clinical Characteristics.

Populational aging is marked by chronic noncommunicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarly, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Sex-specific functional effect of IL-12 gene polymorphisms in brain tumours

The role of the IL-12 family cytokines in brain tumourigenesis is an active area of research, but only a few studies have explored the impact of the functional IL12B polymorphisms on brain tumour (BT) risk. The present study aimed to evaluate the possible impact and functional effect of IL12B rs3212227 and rs17860508 on BT susceptibility in adults. We observed a lower frequency of the C-allele variant of the rs3212227 polymorphism among cases with primary BT compared to those with brain metastasis (BrM) and individuals with no benign or malignant tumours under allelic and dominant genetic models. The frequency of the C-allele of rs3212227 was significantly lower in primary BT cases than in controls (16% vs. 26.5% with OR = 0.529, 95%CI: 0.3–0.94, p = .029; ORadjusted=0.442; 95%CI: 0.23–0.87; p = .018). There was no significant association between rs17860508 and BT risk under all analysed genetic models after age and sex adjustment. A significantly higher IL-12p40 serum level in men with primary BT than in women (p = .0007) was found. We observed a sex-specific effect of rs3212227 polymorphism on serum IL-12p40 levels in cases with primary BT in contrast to BrM. The C-allele carriership was associated with higher IL-12p40 in women with primary BT. Serum levels of IL-23 were similar across the patients’ subgroups. The obtained results suggest that the IL12B rs3212227 polymorphism influences the risk for primary BT in contrast to rs17860508 polymorphism and shows a sex-specific functional effect on IL-12p40 levels. Also, the male gender was associated with higher IL-12p40 in cases with primary BT.

The Impact of IL1B rs1143634 and DEFB1 rs11362 Variants on Periodontitis Risk in Phenylketonuria and Type 1 Diabetes Mellitus Patients in a Latvian Population.

Periodontitis is a multifactorial disease that affects approximately 11% of the global population. The objective of this study was to examine whether, among individuals with phenylketonuria and type 1 diabetes mellitus, those with the IL1B rs1143634 and/or DEFB1 rs11362 genetic variants exhibit a higher periodontitis risk compared to healthy controls. In all, 43 phenylketonuria patients (aged 12-53), 28 type 1 diabetes mellitus patients (aged 11-40), and 63 healthy controls (aged 12-53) were included. The evaluation of periodontitis risk was conducted using the Silness-Löe plaque index, the Greene-Vermillion index, and an assessment for the necessity of calculus removal. Genetic variants rs1143634 and rs11362 were genotyped from salivary samples using restriction length polymorphism analysis. The DEFB1 rs11362 variant was associated with higher Silness-Löe and Greene-Vermillion index scores in phenylketonuria patients (p = 0.011 and p = 0.043, respectively). The IL1B rs1143634 variant was associated with lower calculus removal necessity in type 1 diabetes mellitus patients (p = 0.030). Clinical examination showed the worst oral hygiene index scores for PKU patients. PKU patients also reported the least consistent tooth brushing and flossing habits. Genetic associations between DEFB1 rs11362 and IL1B rs1143634 variants and oral hygiene indices were observed in the PKU and T1DM groups, suggesting that genetic factors may contribute to periodontal health differences in these populations. Further research with a larger sample size is needed to confirm these findings and develop targeted oral health interventions.

Polymorphism of IL-12/IL-23 axis is associated with coronary heart disease.

IL12B encodes the shared p40 subunit (IL-12p40) of IL-12 and IL-23, which have diverse immune functions and are closely related to the occurrence and development of atherosclerosis (AS). However, the exact role of IL12B in coronary heart disease (CHD) was still unknown. A case-control association analysis was performed between five single nucleotide polymorphisms (SNPs) of IL12B (rs1003199, rs3212219, rs2569254, rs2853694 and rs3212227) and CHD in Chinese Han population (1824 patients with CHD vs. 2784 controls). Logistic regression analyses were used to study the relationships between SNPs and CHD, while multiple linear regression analyses were used to test the association between the SNP and the severity of CHD. In addition, the plasma IL12B concentration of CHD patients were detected by ELISA. We detected a significant association between one of the SNPs, rs2853694-G and CHD (padj = 2.075 × 10-5 , OR, 0.773 [95% CI, 0.686-0.870]). Stratified analysis showed that rs2853694 was associated with CHD in both male and female populations and was significantly associated with both early- and late-onset CHD. In addition, rs2853694 is also related to the different types of CHD including clinical-CHD and anatomical-CHD. Moreover, there are significant differences in serum IL12B concentrations between rs2853694-TT carriers and rs2853694-GT carriers in CHD patients (p = 0.010). A common variant of IL12B was found significantly associated with CHD and its subgroups. As a shared subunit of IL-12 and IL-23, IL-12p40 may play a key role in IL-12/IL-23 axis mediated AS, which is expected to be an effective therapeutic target for CHD.

Design of a prognostic model for assessing the risk of developing asbestosis based on the results of molecular genetic studies

Introduction. Preventive measures, including the development of a system for diagnosing early signs of changes in the health status of employees and predicting individual risks of developing the disease, aimed at preserving labor resources, reducing disability and extending working life expectancy, are an absolute priority in the field of occupational safety.&#x0D; The aim of the study to develop a prognostic model of the risk of developing asbestosis based on molecular genetic studies in employees of enterprises for the extraction and enrichment of chrysotile asbestos.&#x0D; Materials and methods. Based on studies previously conducted in the Laboratory of Biomedical Research at the Izmerov Research Institute of Occupational Health, scientists have identified a set of informative and significant single-nucleotide polymorphic gene variants for use as predictors in the construction of a prognostic model in the development of asbestos in workers of enterprises for the extraction and enrichment of chrysotile asbestos. We examined 136 people who worked at the enterprise for the extraction and enrichment of chrysotile asbestos. The researchers formed two groups comparable in terms of work experience, dustiness, age and gender: 68 former employees of the main production specialties with an established diagnosis of asbestos and 68 workers without bronchopulmonary pathology.&#x0D; The authors calculated the exposure dose of chrysotile-containing dust and calculated it taking into account the percentage of time spent at the workplace, and also performed a molecular genetic study of single-nucleotide polymorphic variants of the genes IL-1β rs16944, IL-4 rs2243250, TGF-β1 rs1800471, SOD-2 rs4880 and MMP-9 rs17576.&#x0D; Results. A predictive model has been developed to determine the probability of developing asbestosis in workers of an enterprise for the extraction and enrichment of chrysotile asbestos based on the determination of single nucleotide polymorphisms IL-1β rs16944, SOD-2 rs4880 and MMP-9 rs17576. The results of genetic tests are entered into the formula and if the resulting probability of developing asbestosis is equal to or higher than the threshold (0.582), the employee is included in the high-risk group. The sensitivity and specificity of the developed model were 70.1% and 70.6%, respectively.&#x0D; Conclusion. Molecular genetic indicators can act as predictors in the development of asbestosis in workers of the chrysotile extraction and enrichment industry and can be used to form high-risk groups during preventive measures.&#x0D; Ethics. The study was conducted in compliance with ethical standards that guarantee respect for all research subjects and the protection of their health and rights in accordance with the requirements of the Helsinki Declaration of the World Medical Association. All persons included in the study gave informed voluntary consent to the examination in accordance with Federal Law No. 323-FZ dated 11/21/2011 "On the Basics of Public Health Protection in the Russian Federation". The study was approved by the conclusion of the local Ethics committee of Izmerov Research Institute of Occupational Health (minutes of the meeting of the Ethics committee of Izmerov Research Institute of Occupational Health No. 9 dated 11/29/2016).

Genetic predictors of abdominal complications after cardiac surgery: a prospective study

Introduction: The prediction of postoperative abdominal complications is a continuing concern in the cardiac surgery. Identifying genetic predictors will allow a better understanding of the pathophysiological mechanisms underlying postoperative disorders and their prevention.Objective: To identify genetic predictors of abdominal complications after heart surgery.Methods: A prospective study was carried out at the Federal Center for Cardiovascular Surgery (Chelyabinsk) involving 72 patients with abdominal complications and 102 controls without such complications. The distribution of genotypes was assessed for adherence to the Hardy-Weinberg distribution using the exact method according to the SNP-HWE algorithm in the PLINK package (version 1.9). To identify marker genes associated with the risk of abdominal complications, 6 models were evaluated for each polymorphic gene: allelic, codominant, dominant, recessive, overdominant, and log-additive. To analyze the SNPs of the IL6 (rs1800795), TNF (rs1800629), and SERPINE1 (rs1799768) genes, real-time polymerase chain reaction (PCR) was performed on a Rotor-Gene 6000 detecting cycler (Corbett Research Pty Ltd., Mortlake, Australia) using primers and probes manufactured by Syntol CJSC (Moscow, Russia) according to the manufacturer's instructions. To analyze the SNPs of the IL1B (rs1143634), CXCL8 (rs4073), IL10 (rs1800872), APOE (rs429358), FABP2 (rs1799883), NOS3 (rs1799983), VEGFA (rs699947) genes, real-time PCR was performed on a DTprime 4 analyzer (DNA-Technology, Moscow, Russia) using primers and probes manufactured by TestGene LLC (Ulyanovsk, Russia) according to the manufacturer's instructions. The determination of the SNP of the TLR3 gene (rs3775291) relied on real-time PCR according to melting curves using TestGene LLC reagent kits on a DTprime 4 device.Results: Two genes, IL1B rs1143634 and FABP2 rs1799883, were found to be associated with the risk of abdominal complications. Following the adjustment for multiple comparisons, only FABP2 rs1799883 remained statistically significant. The rs1799883 polymorphism of the FABP2 gene can be considered a predictor of the risk of abdominal complications and can be evaluated within the codominant and dominant models, which exhibit similar p-values (0.003 and 0.002, respectively). Overall, the analysis of the obtained data suggests that the risk of abdominal complications is associated with the presence of the mutant allele C in the genome, likely due to its dominance. Specifically, in the dominant model, the odds ratio was 3.53 (95% CI 1.62 to 7.70).Conclusion: The most significant markers of the risk of abdominal complications were the IL1B (rs1143634) and FABP2 (rs1799883) genes, of which FABP2 (rs1799883) remained statistically significant after adjusting for multiple comparisons. Its polymorphism as a predictor of abdominal complications can be evaluated within the codominant and dominant models. Received 13 June 2023. Revised 28 November 2023. Accepted 29 November 2023. Funding: The study was supported by the Russian Science Foundation, project No. 22-25-20016, https://rscf.ru/project/22-25-20016/ Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: O.S. Abramovskikh, A.A. Fokin, D.V. BelovData collection and analysis: Yu.V. LoginovaStatistical analysis: M.A. ZotovaDrafting the article: D.V. BelovCritical revision of the article: Yu.V. LoginovaFinal approval of the version to be published: D.V. Belov, O.S. Abramovskikh, M.A. Zotova, Yu.V. Loginova, A.A. Fokin

The Disease Model of Addiction: The Impact of Genetic Variability in the Oxidative Stress and Inflammation Pathways on Alcohol Dependance and Comorbid Psychosymptomatology.

Oxidative stress and neuroinflammation are involved in the pathogenesis of alcohol addiction. However, little is known regarding the effect of genetic, behavioral, psychological, and environmental sources of origin on the inflammation and oxidative stress pathways of patients with alcohol addiction. Our study aimed to evaluate the impact of selected common functional single-nucleotide polymorphisms in inflammation and oxidative stress genes on alcohol addiction, and common comorbid psychosymptomatology. Our study included 89 hospitalized alcohol-addicted patients and 93 healthy individuals, all Slovenian males. Their DNA was isolated from peripheral blood and patients were genotyped for PON1 rs705379, rs705381, rs854560, and rs662, SOD2 rs4880, GPX1 rs1050450, IL1B rs1143623, rs16944, and rs1071676, IL6 rs1800795, IL6R rs2228145, and miR146a rs2910164. Kruskal-Wallis and Mann-Whitney tests were used for the additive and dominant genetic models, respectively. Our findings suggested the involvement of IL6 rs1800795 in alcohol addiction. Moreover, our data indicated that the genetic variability of SOD2 and PON1, as well as IL1B and IL6R, may be related to comorbid psychosymptomatology, revealing a potential indirect means of association of both the oxidative stress and inflammation pathways.

Promoter polymorphisms of neuropeptide Y, interleukin-1B and increased IL-1β levels are associated with rheumatoid arthritis susceptibility in South Gujarat population

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction. Interleukin-1B(IL-1β) has been implicated in RA, and neuropeptide Y (NPY) induces the release of pro-inflammatory cytokines including IL1-β, TNF-α and IL-6. Single nucleotide polymorphisms (SNPs) in NPY and IL1B gene may lead to their altered levels leading to RA pathogenesis. Therefore, we aimed to investigate association of NPY rs16147(T > C) SNP, and genotype–phenotype correlation of the IL1B rs16944(C > T) SNP in 302 RA patients and 337 controls by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Both the genotype and allele frequencies for NPY rs16147(T > C)(p = 0.0019 &p = 0.012) and IL1B rs16944(C > T)(p = 0.0024 &p = 0.0014) SNPs differed significantly between RA patients and controls. The odds ratios of 1.23 and 1.47 for NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs respectively, suggest that these SNPs may be genetic risk factor for RA in South Gujarat population. The plasma IL-1β levels(p = 0.0332) and genotype-phenotype correlation of IL1B rs16944(C > T) SNP suggested increased IL-1β levels, particularly in patients with susceptible ‘TT' genotypes(p < 0.0001). Additionally, plasma IL-1β level was significantly increased in severe RA patients (p = 0.0025) and positively correlated with Rheumatoid factor(RF) (r = 0.9240, p < 0.0001), suggesting the role of IL-1β in disease severity. Overall, the study for the first time suggests that NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs may be associated with RA susceptibility in South Gujarat population. Additionally, the IL1B rs16944 susceptible ‘TT' genotype may lead to increased IL-1β levels, thereby contributing to RA pathogenesis and severity.

Impact of IL-6 and IL-1β Gene Variants on Non-small-cell Lung Cancer Risk in Egyptian Patients

Lung cancer is a serious health and life issue, with the fastest-growing incidence and fatality rates worldwide. It is now clear that inflammation is a key factor involved in all aspects of carcinogenesis, notably lung cancer development. Genetic changes, including polymorphisms in inflammatory genes, are supposed to be a significant cause of increased lung cancer risk. The main idea of this research was to disclose the linkage between both IL-6 rs1800795 and IL-1β rs16944 variants and susceptibility to non-small-cell lung cancer (NSCLC) in Egyptians. This case–control design was composed of 127 cases and 138 controls, which were genotyped using the ARMS-PCR technique. To examine the NSCLC susceptibility under various genetic models, the odds ratio (OR) and 95% confidence intervals (CIs) were determined by logistic regression. Rs1800795 of the IL-6 gene was linked to higher odds of NSCLC under the allele model (adjusted, OR 2.28; 95% CI 1.2–4.33; p = 0.011). In the genetic models, IL-6 rs1800795 elevated the odds of NSCLC, while IL-1β rs16944 decreased the odds of NSCLC. Stratification analysis showed that IL-6 rs1800795 greatly increased the NSCLC risk in females and adenocarcinoma subtypes, whereas IL-1β rs16944 largely decreased the NSCLC risk for males, patients aged < 55, and nonsmokers. Regarding clinical data, the IL-6 variant was remarkably correlated with tumor size. This work primarily established that IL-6 and IL-1β variants have a great impact on NSCLC development in the Egyptian population; thus, it may be a supportive guide for earlier NSCLC prevention.

Association of IL-1β rs16944 and IL-1RN rs2234663 gene polymorphisms with graft function in renal transplant recipients

BackgroundAfter renal transplantation, renal graft function affects both patient and graft survival. There is growing evidence of the genetic association between interleukin-1β (IL-1β) or its receptor antagonist (IL-1RN) and graft function in renal transplantation. The objective of this study is to investigate the role of the recipient IL-1β and IL-1RN gene polymorphisms and their haplotypes on renal graft outcome.MethodsUsing PCR, IL-1β (− 511C/T) and IL-1RN (86 bp VNTR) gene polymorphisms were determined in 31 renal allograft recipients; eight cases with stable allograft function and 23 cases with early renal dysfunction as well as 26 age- and gender-matched healthy controls.ResultsA statistically significant difference in IL-1 β (− 511C/T) gene polymorphisms and IL-1RN/IL-1β haplotypes was observed on comparing renal allograft recipients with stable allograft function and those with early renal allograft dysfunction. However, the difference in the frequency distribution of IL-1RN gene polymorphisms, between these two groups, did not reach statistical significance. Also, no statistically significant difference was observed in comparing these two gene polymorphisms and their haplotypes between renal allograft recipients and healthy controls.ConclusionThe IL-1β − 511 CT/TT polymorphic genotypes and IL-1RN/IL-1β polymorphic haplotypes are associated with early renal allograft dysfunction. These are observational data that can be repeated in larger studies. If the results obtained are consistent, this might open doors to personalized medicine where clinicians can take necessary measures to identify the renal transplant recipients’ genotypes at risk of mounting an increased inflammatory response and hence administer the appropriate immunosuppressive protocol.

Polymorphism of cytokine and C-reactive protein genes in patients with psoriasis in the Kemerovo region of Russia

Aim. To study the associations of polymorphisms of IL-1b (rs16944), IL-6 (rs1554606), IL-8 (rs2227306), IL-10 (rs1800896), TNFα (rs361525), CRP (rs1205) genes and their intergenic interactions with the risk of psoriasis development in Kemerovo region residents. Materials and Methods. We examined 170 patients (102 men and 78 women) a clinically established diagnosis of vulgar psoriasis. The average age of patients was 46.2+3.9 years, 165 people (97%) had progressive stage psoriasis. The control group (n=155) included 98 healthy men and 57 women matched by age. Genomic DNA isolated from peripheral blood leukocytes by phenol-chloroform extraction according to the standard protocol was used as material. Logistic regression analysis was performed to assess the role of intergenic interactions in the development of psoriasis. Conclusion. In patients of the Kemerovo region, vulgar psoriasis is associated with minor homozygous genotypes of polymorphic variants of TNFα (rs361525), IL-1b (rs16944), CRP (rs1205) genes. The minor homozygous TNFα (rs361525) genotype has a high odds ratio and is determinant in the development of this form of psoriasis among all genes studied. The major allele and IL-10 genotype (rs1800896) is a disease modifier and affects the clinical course, particularly the development of inflammatory plaques and papules on the lower and upper extremities of patients.