Inflammatory Gene Polymorphisms Research Articles

Inflammatory Response Genes' Polymorphism Associated with Risk of Rheumatic Heart Disease.

Rheumatic heart disease (RHD) caused by group A streptococcus infection is one of the most important reasons of cardiovascular morbidity and mortality in low- and middle-income countries. Aberrant host immune response modulated by polymorphisms in inflammatory response genes plays an important role in RHD pathogenesis. This study aimed to determine risk-associated polymorphic variants in inflammatory response genes in Caucasian RHD patients. A total of 251 Caucasian RHD patients and 300 healthy donors were recruited for this study, and 27 polymorphic sites in 12 genes (TLR1, TLR2, TLR4, TLR6, IL1B, IL6R, IL6, IL10, IL12RB1, IL12B, TNF and CRP) were analyzed using allele-specific PCR. It was demonstrated that the polymorphic variants rs1800871 and rs1800872 in the IL10 gene, rs 1130864, rs3093077 and rs1205 in the CRP gene, rs375947 in the IL12RB1 gene, rs 5743551 and rs5743611 in the TLR1 gene, and rs3775073 in the TLR6 gene can modify RHD risk in a gender- and age-dependent manner. The obtained results can be used to determine the personalized risk of RHD in healthy donors during medical examination or screening, as well as to develop appropriate early prevention strategies targeting RHD in the risk groups.

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.

POLYMORPHISMS IN INFLAMMATORY CYTOKINES NOT ASSOCIATED WITH COGNITIVE TRAJECTORIES IN OLDER ADULTS

Abstract Inflammation and key polymorphisms in inflammatory cytokine genes have been associated with increased Alzheimer’s disease (AD) risk. It is unclear if the same polymorphisms also predict domain-specific cognitive decline, that could eventually lead to AD/dementia, in otherwise healthy older adults. We investigated whether specific single nucleotide polymorphisms (SNPs) in three cytokine genes, IL-1β (rs16944; A or AA at -511), IL-6 (rs1800795; C or CC at -174), and TNFα (rs1800629; A or AA at -308), were associated with differential longitudinal trajectories of global cognitive function, episodic memory, attention and working memory, and executive function. Participants were 324 non-demented older adults (Mage=72.8 years at first visit, SD=6.09, age range 57-92 years) who completed 9 research visits, on average. Slopes were examined after adjustment for baseline age, sex, education, conversion to MCI or dementia during study, and APOE ɛ4 status. Findings indicated no statistically significant relationships between the SNPs of interest and longitudinal trajectories (spanning up to 16 years) of cognitive functioning in any cognitive domain examined. Other factors related to AD may be necessary for these SNPs to have significant brain-related effects. Attempts were made to further validate the non-significant findings by conducting post-hoc analyses to determine whether these SNPs were associated with plasma biomarker levels in this sample of healthy older adults. However, variability between and within the assays precluded confidence in the results. Further research is needed to determine whether these SNP genotypes are associated with concentrations of their respective blood-plasma biomarkers in non-demented older adults.

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.

Identifying Inflammatory Pathways That Promote RBC Alloimmunization in Patients with Sickle Cell Disease

Introduction: During red blood cell (RBC) transfusion, exposure to unmatched non-ABO antigens can lead to production of alloantibodies that promote potentially fatal hemolytic events. Patients with Sickle Cell Disease (SCD) have the highest incidence of RBC alloimmunization. Prior studies indicate that an altered immuno-regulatory and/or pro-inflammatory state may determine the risk of RBC alloimmunization. For example, one study reported that patients with SCD have inflammatory cytokine gene polymorphisms that could be associated with diverse disease presentations and alloimmunization. We previously reported that inflammatory type 1 interferons (IFNα/β) produced by innate immune cells are required for RBC alloimmunization in mice, while others have suggested that NFkB-induced cytokines play a role in murine transfusion models. However, the inflammatory factors that regulate RBC alloimmunization in patients with SCD are poorly understood. Alloimmunized patients with SCD also have elevated levels of anti-RBC autoantibodies, which facilitate erythrophagocytosis. Given the role of erythrophagocytosis by spleen macrophages in processing RBC antigens, we hypothesized that erythrophagocytosis of SCD RBCs may promote inflammatory pathways that regulate alloimmune responses. Methods: RBCs from control subjects (AA), and reticulocytes and mature RBCs from patients with SCD, were opsonized or not with anti-RBC antibodies (anti-RhD) and co-cultured for 3 hrs with human macrophages (hMac) differentiated from monocytes of healthy subjects. Phagocytosis of labeled RBCs was analyzed by flow cytometry. Bulk mRNA sequencing of co-cultured macrophages was performed to identify differential gene expression. Ingenuity Pathway Analysis (IPA) software was used to identify relevant pathways and upstream regulators of differentially expressed genes. To validate sequencing results, cytokine levels from co-culture supernatants were measured by multiplex cytokine assays. Results: Flow cytometric analysis revealed that opsonization was required for erythrophagocytosis in an FcR dependent manner. RNA-seq Differential Expression analysis of macrophages co-cultured with AA opsonized RBCs vs. non-opsonized RBCs identified 166 significantly upregulated and 24 downregulated genes (p&amp;lt;0.0001). IPA analysis revealed that the top 12 canonical pathways were related to inflammation, including TNF, IL-17, NF-kappa-B and NOD-like receptor signaling pathways. TNF signaling was the top predicted upstream regulator pathway with a fold enrichment score of 10.3 (16 genes) (p&amp;lt;0.0001). Co-cultures of mature RBCs from patients with SCD showed comparable results. When comparing macrophages from co-cultures of opsonized reticulocytes vs. non-opsonized reticulocytes from patients with SCD, 174 genes were upregulated and 31 were downregulated (p&amp;lt;0.0001). Pathway analysis also revealed unique signatures for opsonized reticulocytes from patients with SCD. The top 12 canonical pathways included TNF, NF-kappa-B and NOD-like receptor signaling pathways (Figure 1). The top predicted upstream regulators were TNF and the NF-kappa B signaling pathway with a fold enrichment score of 12.3 (22 genes) (p&amp;lt;0.0001) and 10.9 (18 genes), respectively (Figure 1). Finally, to validate the sequencing results, cytokines levels from supernatants of hMac co-cultures with the RBCs from the patients with SCD and control subjects were measured. Erythrophagocytosis of opsonized reticulocytes and AA RBCs, compared to non-opsonized co-cultures, led to production of NFκB-mediated cytokines, including TNF. Our results show that erythrophagocytosis of SCD RBCs promote NFκB-mediated TNF production. These results warrant further investigation of the role of NFκB-mediated inflammation in RBC alloimmunization in patients with SCD.

Increased Frequencies of the ‒174G and ‒572C IL6 Alleles in Populations of Indigenous Peoples of Siberia Compared to Russians.

Abstract-The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants ‒174G/C (rs1800795) and ‒572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the ‒174G and ‒572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.

Polygenic Analysis of Cytokine and Inflammatory Gene Polymorphisms in Chronic Obstructive Pulmonary Disease

Polygenic Analysis of Cytokine and Inflammatory Gene Polymorphisms in Chronic Obstructive Pulmonary Disease

Increased Frequencies of the -174G and -572C IL6 Alleles in Populations of Indigenous Peoples of Siberia Compared to Russians

The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants -174G/C (rs1800795) and -572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the -174G and -572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.

Генетический полиморфизм воспалительных цитокинов в крови пациентов с инвазией Opisthorchis felineus

Aim: To research the relationship between laboratory and instrumental manifestations of pathology and polymorphisms of inflammatory cytokine genes in patients with Opisthorchis felineus invasion. Design. During 2022, we conducted a comparative study of patients who were hospitalized for etiotropic therapy of O. felineus invasion. Materials and methods. 139 patients with O. felineus invasion were examined. All patients underwent clinical and biochemical blood tests, ultrasound of the abdominal organs and liver elastometry with an assessment of liver fibrosis according to the METAVIR scale. Genotyping of single nucleotide polymorphisms of the IL28b, IL6, TNFA, and IFNG genes was performed using real-time PCR. Results. In patients with opisthorchiasis, liver fibrosis was associated with the presence of the minor allele A of the rs1800630 TNFA polymorphism and the TC genotype of rs2069705 IFNG. Polyps in the gallbladder were associated with the CC genotype of rs1800630 TNFA, while an increase in alkaline phosphatase and an increase in the proportion of eosinophils in the blood were associated with the CC genotype of rs2069705 IFNG. We did not find differences in the studied parameters depending on the genetic polymorphisms rs12979860 IL28b and rs1800795 IL6 in patients with O. felineus invasion. Conclusion. The obtained regularities should be used to increase the efficiency of dispensary observation in order to prevent the development of complications of parasitic invasion. Keywords: Opisthorchis felineus, single nucleotide polymorphism, cytokines, liver fibrosis.

The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population.

BackgroundKawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported.MethodsA total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance.ResultsBoth of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06–3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10–2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62–4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37–3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22–2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24–2.27, p = 0.0008).ConclusionOur findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.

Association between innate immunity gene polymorphisms and neonatal sepsis development: a systematic review and meta-analysis.

The aim of this meta-analysis was to analyze all available data from studies investigating associations between polymorphisms in genes responsible for innate immunity and neonatal sepsis development. A comprehensive literature search, reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-S guidelines, was performed with no language restriction. Studies derived using the PICO (population, intervention, comparison and outcomes) strategy, with data on the genotype distribution for innate immunity gene polymorphisms in newborns withandwithout sepsis. Data were analyzed using Review Manager. The Cochran-Mantel-Haenszel test was used to calculate odds ratios with 95% confidence intervals. Heterogeneity was tested using the I2 index. From a total of 9428 possibly relevant articles, 33 qualified for inclusion in this systematic review. According to the STrengthening the REporting of Genetic Association Studies, 23 studies were found to be of moderate quality, while 10 were of low quality. The results showed an association of the mannose-binding lectin (MBL) exon1 genetic polymorphism with the risk of culture-proven sepsis. Toll-like receptor (TLR) 4 rs4986791 genotype distribution suggests its association with the increased risk of culture-proven sepsis. The certainty of evidence per GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) varied from very low to low. Publication bias was not detected. Out of the 11 investigated single-nucleotide polymorphisms, this meta-analysis found a possible association between the risk for culture-proven sepsis and MBL exon1 and TLR4 rs4986791polymorphisms. There is an evident need for larger well-designed, multicentric observational studies investigating inflammatory gene polymorphisms in neonatal sepsis.

Abstract P123: IL1RN Gene Polymorphism And The Development Of Acute Myocardial Infarction In Young Patients

IL-1RA is a member of the interleukin-1 cytokine family. IL1Ra is secreted by various types of cells, including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1. This protein inhibits the activity of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B) and modulates various interleukin 1-related immune and inflammatory responses. Hypothesis: The aim of this study was to investigate the relationship between IL1RN gene polymorphism and the development of acute myocardial infarction (AMI) in young patients. Material/methods: In a case-control study, we investigated polymorphisms in the IL1RN gene (rs4251961) using quantitative real-time polymerase chain reaction analysis. The study was conducted with AMI (age range: 36 to 55 years; mean: 42.74 ± 12.47 years) with 11 healthy people in the control group. We also studied the interaction between genetic polymorphism and inflammatory agents such as CRP, IL 1, IL 6. All indicators were calculated using the statistical program Statistica 12.0, a P-value &lt;0.05 was considered statistically significant. Results: Statistically significant differences in the distribution of rs4251961 genotypes were observed between the two groups. Carriers of the T allele had a significantly higher risk of developing AMI than carriers of the C allele (P &lt;0.05). Subjects carrying the TT and TC haplotypes have a significantly increased incidence of coronary artery disease. We also found that the CYP1B1 rs1056836 polymorphism had a synergistic effect with CRP levels on the risk of coronary heart disease. Conclusions: The rs4251961 gene polymorphism is closely associated with the development of AMI in patients with coronary artery disease. There is a mutual synergistic effect between the inflammatory response and IL1RN gene polymorphism in relation to the development of CAD complications. Functional polymorphisms of the IL1RN gene can affect the susceptibility and progression of CAD, increase the pro-inflammatory response, and destabilize the atherosclerotic plaque.

Polymorphisms in the IL1-b gene are associated with increased Glu and Glx levels in treatment-resistant depression

• Metabolic alterations in the ventromedial prefrontal region were examined in depressed patients employing imaging genetics • Polymorphisms in inflammatory genes might be associated with increased Glutamate and Glx levels in difficult to treat depressed patients • Increase in treatment resistance score might be associated with changes in metabolites’ levels • There is an interaction between genotype and resistance score manifesting in elevated glutamatergic metabolic levels in treatment resistant patients

Analysis of propensity score matching between inflammatory factor levels and gene polymorphisms and susceptibility to obstructive sleep apnea

Objective:To explore the correlation between the levels of inflammatory factors and their gene polymorphisms and the susceptibility to obstructive sleep apnea（OSA）. Methods:Seventy-nine patients who were diagnosed with OSA in People's Hospital of Xinjiang Uygur Autonomous Region from October 2018 to December 2020 were selected as the study group, and 104 healthy adults who received physical examination during the same period were selected as the control group. After collecting the clinical data of the two groups of patients, the two groups of patients were matched by propensity scores. Then, the serum IL-6, IL-8 and TNF-α levels and the peripheral blood IL-6, IL-8 and TNF-α gene polymorphism analysis and comparison were performed on the included matched patients. Results:Before matching, the age, proportion of males, BMI, neck circumference, smoking history, SBP and DBP of the study group were higher than those of the control group, and the difference was statistically significant（P<0.05）. After the two groups of patients were matched by propensity scores, a total of 67 patients were successfully matched. The covariates between the two groups were all balanced after matching, and the balance of the PSM covariates was significantly improved（P>0.05）. After matching, the fasting blood glucose, C-reactive protein, IL-6, IL-8, TNF-α, AHI and Ts90% of the study group were significantly higher than those of the control group, and the difference was statistically significant（P<0.05）. Hardy-Weinberg balance verifies that the gene frequencies of each group are in accordance with the genetic balance rule（P>0.05）; after matching, the distribution of IL-6（rs1800795） and TNF-α（rs1800629） genotypes between the two groups is compared, and the difference is statistically significant scientific significance; the frequency of IL-6（rs1800795） allele C and the frequency of TNF-α（rs1800629） allele A in the study group were significantly higher than those in the control group, and the difference was statistically significant（P<0.05）. Conclusion:The levels of inflammatory factors TNF-α and IL-6 and their gene polymorphisms are significantly related to the susceptibility to OSA.

Association of Immune and Inflammatory Gene Polymorphism With the Risk of IgA Nephropathy: A Systematic Review and Meta-Analysis of 45 Studies.

IgA nephropathy is the most prevalent primary glomerulonephritis worldwide, with identical immunopathological characteristics caused by multiple etiologies as well as influenced by geographical and ethnical factors. To elucidate the role of immunologic and inflammatory mechanisms in the susceptibility to IgA nephropathy, we explored single nucleotide polymorphisms of related molecules in the immune pathways. We searched the PubMed database for studies that involved all gene variants of molecules in the 20 immunologic and inflammatory pathways selected from the Kyoto Encyclopedia of Genes and Genomes database. The odds ratios with their corresponding 95% confidence intervals in six genetic models (allele model, dominant model, homozygote model, heterozygote model, overdominant model, and recessive model) were summarized using fixed or random effect models. Subgroup analysis was conducted based on different ethnicities with generalized odds ratios. Heterogeneity was evaluated using the Q and I2 tests. Begg’s funnel plot and Egger’s linear regression test were used to evaluating possible publication bias among the included studies, and sensitivity analysis was used to test the stability of the overall results. A total of 45 studies met our selection criteria and eight related genetic association studies were retrieved, including 320 single-nucleotide polymorphisms from 20 candidate pathways, ranging from 2000 to 2021. A total of 28,994 healthy people versus 20,600 IgA nephropathy patients were enrolled. Upon meta-analyzed results that TGFB1 (rs1800469, rs1982073, rs1800471), IL-1B (rs1143627), IL-18 (rs1946518), and TLR1 (rs5743557) showed effect with or without ethnicity difference. And 10 variants presented stable and robust related to IgA nephropathy. This research showed that genetic variants are related to the immunologic and inflammatory effects of IgA nephropathy pathogenesis. The meta-analysis results supported the previous researches, and may help deepen the understanding of pathogenesis and explore new targets for IgA nephropathy-specific immunotherapy.

Associations between Inflammatory Cytokine Gene Polymorphisms and Susceptibilities to Intracranial Aneurysm in Chinese Population

Intracranial aneurysm (IA) is a complex disease caused by genetic and environmental factors. Evidence indicates that inflammation plays an important role in IA occurrence. We aimed to explore the associations between inflammatory cytokine gene polymorphisms and IA in a Chinese population. This study enrolled 768 participants of Han ethnicity, including 384 patients with IA and 384 healthy individuals. Sixteen single nucleotide polymorphisms (SNPs) of IL1, IL6, IL12, and TNF-α genes were genotyped using the Sequenom MassARRAY platform. Univariate and multivariate logistic regression analyses were used to analyze the associations. We found IL12B rs3181216 was significantly associated with IA in the recessive and additive models (OR = 0.46, 95% CI = 0.23–0.89, P = 0.022; OR = 0.74, 95% CI = 0.56–0.98, P = 0.034, respectively). TNF-α rs1799964 was associated with IA in dominant and additive models (OR = 0.67, 95% CI = 0.46–0.98, P = 0.041; OR = 0.71, 95% CI = 0.51–0.98, P = 0.034, respectively). IL1A rs17561 was associated with single IA susceptibility (dominant model: OR = 0.52, 95% CI = 0.31–0.85, P = 0.040). The IL12B rs3181216 polymorphism was associated with single IA susceptibility in the recessive model (OR = 0.41, 95% CI = 0.18–0.93, P = 0.033). The IL12B rs2195940 polymorphism was associated with multiple IAs susceptibility (dominant model: OR = 0.28, 95% CI = 0.09–0.89, P = 0.031; additive model: OR = 0.28, 95% CI = 0.09–0.90, P = 0.032). TNF-α rs1799964 was associated with multiple IAs susceptibility in the dominant model (OR = 0.54, 95% CI = 0.30–0.97, P = 0.040). No associations were found between other polymorphisms and IA susceptibility. Therefore, IL1A, IL12B, and TNF-α gene polymorphisms are associated with IA susceptibility in a Chinese population.

Association Study between Proinflammatory Cytokine Gene Polymorphism and Risk of Recurrent Spontaneous Abortion

To investigate the correlation between inflammatory cytokine gene polymorphisms and the risk of recurrent miscarriage. A total of 120 patients with recurrent spontaneous abortion in our hospital between January 2019 and December 2020 were selected as the recurrent spontaneous abortion group and 120 healthy pregnant women with early pregnancy who visited the hospital during the same period were used as the control group and the genotype of interleukin-18 was detected by single nucleotide polymorphism typing technique and the validation method was Hardy Weinberg’s law of genetic equilibrium was used to verify the genotype of interleukin-18 and the relationship between interleukin-18 genotype and the risk of recurrent spontaneous abortion was analyzed by logistic method. The results showed that the level of interleukin-18 in the recurrent spontaneous abortion group was significantly higher than that in the control group (p 0.05); the interleukin-18 (rs1946519) and interleukin- 18(rs360717) in the control group The actual genotype frequencies of interleukin-18(rs1946519) and interleukin-18 (rs360717) in the control group were also not significantly different from the theoretical values (test values were 0.474 and 0.153, p>0.05); the genotypes of the rs1946519 and rs360717 loci showed significant differences and the recurrent spontaneous abortion group had significantly more A alleles than the control group (p<0.05); rs1946519 and rs360717 locus mutant cases showed significant differences in serum interleukin-17 levels, with AA and TT genotypes showing higher concentrations than other genotypes, respectively (p<0.05); the relative risk of recurrent spontaneous abortion risk in rs1946519 AG and AA gene carriers was 2.468 and 2.468 times higher than that of the GG allele, respectively. The relative risk of recurrent spontaneous abortion in rs360717 TC and TT gene carriers was 1.973 and 1.545 times higher than that of CC allele, respectively and all of them had higher risk of recurrent spontaneous abortion (p<0.05). The rs1946519 polymorphic allele G and rs360717 allele C mutations of interleukin-18 affect the serum hormone levels of patients and lead to an increased risk of recurrent spontaneous abortion in pregnant women. Therefore, interleukin-18 gene polymorphisms may be an important basis for the pathogenesis of recurrent spontaneous abortion and its treatment.

Association of polymorphisms in inflammatory cytokine genes with the development of head and neck cancer in Pakistani population

Head and neck cancer (HNC) is the most common type of carcinoma and represents a major health problem in developing countries. HNC is a multifactorial condition associated with a variety of risk factors comprising genetic, environmental and life style. Genetic polymorphisms of interleukin genes might contribute to the development of HNC. Present study was conducted to investigate a possible association of HNC with single nucleotide polymorphisms (SNPs) in interleukin genes (IL-8 rs4073 A/T, IL-4 rs2070874 C/T, IL-10 rs1800896 T/C, IL-10 rs180072 T/G, IL-6 rs1800796 C/G, IL-6 rs1800795 C/G, and IL-1-α rs17561 A/C) and oral hygiene in Pakistani Population. For this purpose, 231 cases and 219 controls were recruited. The SNPs were assessed through QuantStudio real time PCR system. Analysis of the data showed a significant association of IL-10 rs1800896 with HNC while other SNPs were not associated was HNC pathogenicity. Further, no significant association was observed between hygiene associated factors and HNC in the studied population. This study presents useful aspects of HNC in Pakistani cohort.

Correlation Study of the Long-Term Prognosis of Venous Thromboembolism and Inflammatory Gene Polymorphisms.

BackgroundVenous thromboembolism (VTE) is the third most common cause of cardiovascular death worldwide, following coronary heart disease and stroke, and many risk factors for VTE are not yet clear. Our study investigated the association between multiple inflammatory gene polymorphisms and VTE prognosis, aiming to find a new predictor of VTE prognosis.MethodsBased on our previous studies, we detected the plasma levels of serum amyloid A protein (SAA), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) and their 8 gene polymorphisms by ELISA and a multiplex ligation detection reaction (iMLDR) method in 284 patients with VTE. All subjects were followed up for 5 years.ResultsThe 5-year follow-up results of this study showed that 62 of the 284 patients (21.83%) had reached the endpoint (all-cause death). Kaplan–Meier survival analyses revealed that the mortality rate of VTE patients with a high Simplified Pulmonary Embolism Severity Index (SPESI) score and carrying IL-1 rs1800587 mutation genotypes was significantly increased (log-rank p=0.000 and 0.034 respectively). The multifactor Cox regression results confirmed that the mortality rate of patients who carrying IL-1 rs1800587 mutation genotypes was significantly increased (HR=2.982; 95% CI: 1.681–5.100). The mortality rate of those carrying IL-1 rs1143634 mutation genotypes was significantly decreased (HR=0.294; 95% CI: 0.132–0.652). There were no significant differences in mortality rates between wild-type and mutant genotypes of IL-1 rs1143634, IL-1 rs2234650, SAA rs11603089, and TNF-α rs1800629 (P>0.05).ConclusionA high SPESI score and the presence of the IL-1 rs1800587 mutant genotype predict shorter survival in patients with VTE, whereas the IL-1 rs1143634 genotype is associated with a lower mortality rate. Screening for mutations in inflammation-related genes has prognostic value in the clinical management of VTE.

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.