IL-10 Polymorphisms Research Articles

Gene polymorphism of IL6, DHCR7, VDR, CYP2R1, GC in polycystic ovary syndrome and autoimmune thyroiditis

Polycystic ovary syndrome is a common pathology in women of reproductive age, leading to hyperandrogenism, dyslipidemia, diabetes mellitus, ovulation disorder and infertility. Etiopathogenesis of the disease is actively studied, but many of its mechanisms are unclear. The aim was to study the frequency of IL6 and vitamin D receptor gene polymorphisms, blood contents of vitamin D in polycystic ovary syndrome combined with autoimmune thyroiditis.A total of 192 women were examined, the average age of the patients was 25.5±3.1 years; of these, 130 women had polycystic ovary syndrome. The patients were divided into 2 groups: with polycystic ovary syndrome combined with autoimmune thyroiditis (1st group) and olycystic ovary syndrome without autoimmune thyroid pathology (2nd group); 62 healthy women made up the control sample. The ELISA method was used to determine thyroid stimulating hormone, thyroid hormones, antibodies to thyroid peroxidase, vitamin D, testosterone, estradiol, progesterone, 17-hydroxyprogesterone, luteotropic hormone, follicle-stimulating hormone. Material for genetic studies was isolated from buccal cells. The typing was performed by PCR, and the following polymorphisms were tested: IL6 (rs1800795 SNP), vitamin D receptor (VDR) gene (rs1544410), DHCR7 (rs12785878), GC (rs2282679), CYP2R1 (rs10741657). The results were as follows: polymorphism of IL6, VDR, DHCR7, GC, CYP2R1 genes was revealed in the patients with polycystic ovary syndrome in combination and without concomitant autoimmune thyroiditis. The lowest levels of 25-hydroxyvitamin D in serum were found in the patients with polycystic ovary syndrome and autoimmune thyroiditis.Polymorphism of IL6 genes, vitamin D receptor, DHCR7, GC, CYP2R1 genes may aggravate the course of polycystic ovary syndrome and requires a more comprehensive study. When polycystic ovary syndrome was combined with autoimmune thyroiditis, the studied gene polymorphisms did not differ significantly from those in patients with polycystic ovary syndrome without autoimmune thyroiditis, thus suggesting greater significance of these genetic factors in pathogenesis of polycystic ovary syndrome. However, more than a half of women with combined endocrine disorders had both homozygous and heterozygous variants of pathological IL6 gene carriage along with lowest vitamin D levels, which may significantly affect immune response and, hence, determine the development of both endocrine disorders.

A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19.

ABSTRACTInterleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients.

Direct Relationship between Interleukin-10 Gene Polymorphism and Hepatocellular Carcinoma Complicated by Direct Acting Antiviral Treatment of Hepatitis C Virus.

Objective:This study aimed to assess the correlation between the genotyping of interleukin-10 (IL-10 polymorphism rs 1800871) and the incidence hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV) treated with direct acting antivirals (DAAs). Method:For 200 patients with HCV infection who completed DAA treatment and followed up for 1 year, IL-10 polymorphism SNP(-819) rs 1800871 analysis was conducted via real time polymerase chain reaction. During the follow-up period, 100 patients who developed HCC were selected and compared with 100 patients who did not develop any complications. Results:The studied patients were divided into two groups according to the incidence of complications after completion of DAA treatments. During the follow-up, 100 patients with HCV infection who developed HCC were selected and compared with 100 patients with HCV infection who did not develop any complications (positive control group). For the HCC group (n = 100), the mean age was 58.1 ± 6.4 years, with 92.7% being male and 7.3% being female; 91% had cirrhosis, 10% had lymphadenitis, 75% had splenomegaly, and 17% had ascites. In the positive control group (n = 100), mean age was 46.3 ± 9.4 years, with 68% being male and 32% being female; 20% had cirrhosis, 12% had splenomegaly, and 4.2% had ascites. The results demonstrated that sofosbuvir (SOF) + daclatasvir + ribavirin regimen was the most prevalent drug treatment for patients with HCC (72%), while SOF + Simeprevir was the most safe treatment for HCV infection among patients with HCC (2%). CT genotype was the most common genotype in the HCC group (56%), among different drug regimen (67.8%). T allele was the most prevalent in HCC group (61%), while the C allele was the least prevalent (39%). Conclusion: IL-10 genotyping may help in selecting the safest and most accurate drug regimen according to the safest genotype response relationship and follow-up of genotype resistance.

The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies

ObjectiveWe performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (−174 G>C, −572 G>C, and −597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. Material and methodsPubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. ResultsFrom 708 identified publications, 33 were used in this analysis. For the −174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28–25.14, ORhomozygous=5.84, 95%CI: 2.06–16.56, ORdominant=7.21, 95%CI: 2.30–22.63, ORrecessive=5.04, 95%CI: 1.78–14.28, ORallelic=6.60, 95%CI: 2.26–19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10–4.81, ORdominant=2.27, 95%CI: 1.22–4.22, ORallelic=2.29, 95%CI: 1.24–4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08–.82, ORrecessive=.25, 95%CI: .08–.80, p<.05). For the −572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16–2.09, ORrecessive=1.63, 95%CI: 1.08–2.45, p<.05). For the −597 polymorphism, no association was observed. ConclusionsHere, the −174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the −572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

IL-6 role in mesial temporal lobe epilepsy development

Inflammation is an epilepsy hallmark with a prominent role assigned to Interleukin-6 (IL-6). This cytokine is claimed to partake in synaptic modulation and neuronal development. IL-6 overexpression has been documented in Mesial Temporal Lobe Epilepsy (MTLE) patients suggesting the influence of IL6 polymorphisms, namely rs1800795 (−174 G > C) in genetic susceptibility to MTLE. We sought to quantify IL-6 brain expression in MTLE patients and analyse the role of rs1800875 polymorphism in epilepsy susceptibility.

The Effects of Cytokine Polymorphisms on Predisposition to Microvascular Complications of Diabetes Mellitus: A Meta-Analysis

Background: It is plausible that gene polymorphisms in tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-18 may affect predisposition to microvascular complications of diabetes mellitus (DM), but the results of the so far published studies remain controversial. Objectives: We conducted this meta-analysis to clarify relationships between TNF-α/IL-1/IL-4/IL-8/IL-18 polymorphisms and predisposition to microvascular complications of DM by pooling the findings of eligible studies. Methods: A comprehensive search of PubMed, Embase, Web of Science, and CNKI was endorsed by us to identify already published studies. Forty-nine studies were found to be eligible for the meta-analyses. Results: The pooled meta-analyses results showed that genotypic frequencies of TNF-α −238 G/A, TNF-α −308 G/A, TNF-α −1,031 T/C, IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −572 G/C, and IL-18 −137 G/C polymorphisms among patients with diabetic nephropathy (DN) and controls differed significantly. Moreover, genotypic frequencies of TNF-α −238 G/A and IL-8 −251 A/T polymorphisms among patients with diabetic retinopathy (DR) and controls also differed significantly. Conclusions: This meta-analysis suggested that TNF-α −238 G/A, TNF-α −308 G/A, TNF-α −1,031 T/C, IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −572 G/C, and IL-18 −137 G/C polymorphisms may affect predisposition of DN. Moreover, TNF-α −238 G/A and IL-8 −251 A/T polymorphisms may affect predisposition of DR.

Is there a correlation between -174(G/C) polymorphism of IL-6 gene and the incidence of acute myocardial infarction?

BackgroundCardiovascular disease (CVD) remains the major cause of death worldwide. Most CVD can be prevented by addressing risk factors. Acute myocardial infarction (AMI) is an inflammatory disorder characterized by changes in several cytokines including the interleukins (ILs). Studies are running to evaluate the genetic variation in the inflammatory system and their influence on the risk factors for CVD aiming for future prevention of this global disease. The aim of the current study was too investigate the association of -174 (G/C) IL-6 polymorphism with the incidence of AMI in a representative sector of the Egyptian population and to examine the contribution of IL-6, as a biomarker, in the pathogenesis of AMI. Genotyping of -174 (G/C) IL-6 polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) while IL-6 levels were assayed by ELISA. ResultsThe genotype distribution of -174 (G/C) IL-6 gene was not significantly different between the control subjects (GG 81.7%, GC 16.3%, CC 1.9%) and the AMI patients (GG 79%, GC 19%, CC 2%).The serum levels of IL-6 were significantly elevated in the AMI patients in comparison to the control subjects (P < 0.0001). ConclusionsThere is no significant association of -174(G/C) polymorphism in the promoter sequence of IL-6 and the incidence of AMI in the examined sample of Egyptian population. Elevated levels of serum IL-6 confirmed the relationship between inflammation and the incidence of AMI.

Association between Interleukin-10 promoter polymorphism with type 2 Diabetes mellitus

Type 2 diabetes mellitus is a multifactorial illness triggered by a complicated interplay of various genetic variants with various environmental variables. The quantity of replicated common genetic variants associated with type 2 diabetes mellitus has increased rapidly with the recent genome-wide association (GWA) research. Major health issue in the public are type 2 diabetes mellitus (T2DM) is common throughout the world. Diabetes mellitus incidence is growing and is anticipated to affect 300 million individuals by 2025. Diabetes has been suggested to alter patterns of cytokine expression as an immune-dependent illness. Insulin resistance (IR) is a disease that results in less than anticipated biological impact of a specified insulin concentration. Insulin resistance and insulin secretion decreased are both defined pathophysiology of T2DM. One of the most alarming health issues of the 21st century is the spread of diabetes around the globe. Our goal in this study was to identify the role of IL-10 polymorphism in T2DM patients. The average age of 60 median patients with type 2 diabetes mellitus (31 males and 29 females) +-SD (45.91667 +-16.08799), fasting blood sugar (FBS) is +-SD (184.25 +-57.76387), hypertension (35 positive/25 negative) and 60 non-diabetic controls (32 males and 28 females) is +- SD (47.31667 +-15.13722). The group (T2DM patients and their control) had not a substantial distinction (P=0.33) and in each group (CC, TT, CT) there was a comparison between IL-10 gene polymorphism. T2DM patients and healthy individuals are not associated with the polymorphism of the gene IL-10 (SNP rs 3021097 (C/T). Keywords: Insulin, Diabetes Mellitis Type 2, Polymorphism, Interleukin-10, Genotype frequencies.

Genotyping of interleukins-18 promoters and their correlation with coronary artery stenosisin Saudi population.

Complex coronary atherosclerotic lesions often lead to coronary occlusion, clinically represented as a single-vessel disease(SVD) and multivessel disease(MVD). These occlusions could hinder the blood flow in coronary arteries that affects appropriate management of the CVD. The current study intended to genotype interleukin (IL)-18 promoter's hotspots (rs187238, rs1946518, and rs1946519) and their possible association with coronary artery stenosis. The IL-18 promoter genotyping was performed by the Sanger method along with the examination of biochemical parameters in 125 study subjects categorized into three groups, viz. controls, SVD and MVD. The current study observed a significant association of diabetes, hypertension, and dyslipidemia between the studied group's viz. healthy controls, SVD, and MVD. Fasting blood sugar and glycosylated hemoglobin (HBA1C) were also significantly enhanced from 4.82 vs. 8.01 and 4.33 vs. 8.27, inSVD, and MVD respectively. Despite the visible differences in the pattern of genotypic and allelic expressions, the current study did not show any statistically significant correlation with IL-18 promoter polymorphism at its hotspots with controls, SVD, and MVD subjects. The only exception of the above results was the distribution of allelic frequency at the rs1946519 hotspot, where a significant change (P < 0.05)was observed. This study is of additional value to our previous reports, revealing the pattern of genotypes and allelic frequency of IL-18 promoters in a small cohort of Saudi ethnicity. Further investigations on larger sample size are recommended to envisage the presence of functional mutations in the IL-18 gene that could establish or rule out the possible association of IL-18 polymorphism with SVD and MVD.

Interleukin-1 and Interleukin-6 Polymorphisms Might Influence Predisposition to Hemorrhagic Cerebral Vascular Diseases: A Meta-Analysis

Background: Interleukin-1 (IL-1) and IL-6 polymorphisms might influence predisposition to hemorrhagic cerebral vascular diseases, but the results of already published studies regarding relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases were still controversial and ambiguous. Objectives: The authors designed this meta-analysis to more precisely estimate the relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases by pooling the results of already published related studies. Methods: The authors searched PubMed, EMBASE, Web of Science, and CNKI for already published studies. Eighteen already published studies were pooled analyzed in this meta-analysis. Results: The pooled meta-analyses’ results showed that distributions of IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms among patients and controls differed significantly. Moreover, distribution of the IL-6 rs1800795 polymorphism among patients and controls from Asians also differed significantly. Further analyses showed similar findings for IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms in aneurysmal subarachnoid hemorrhage (aSAH) subgroup. Conclusions: This meta-analysis suggested that IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms might influence susceptibility to hemorrhagic cerebral vascular diseases, especially for aSAH. Moreover, IL-6 rs1800795 might influence susceptibility to hemorrhagic cerebral vascular diseases in Asians.

Prevalence of Allelic and Genotypic Variants of Il4, Il10, Il12b and Tlr2 Gene Polymorphism in Patients with Chronic Polypoid Rhinosinusitis

Chronic polyposis rhinosinusitis (CPRS) is an important medical and social problem due to its prevalence, combination with other diseases (bronchial asthma, cystic fibrosis), prolonged recurrent course, which leads to a decrease in the quality of life and performance of patients. Bronchopulmonary, rhinogenic orbital and intracranial complications arising against the background of chronic sinusitis not only worsen the quality of life of patients, but also sometimes lead to long-term disability, and sometimes to disability. The results of our study demonstrated that the distribution of the genotypes of polymorphisms of all genes corresponded to the expected, i.e., in this case, the Hardy-Weinberg equilibrium is fulfilled in both groups. Both samples rs2243250 of the IL4 gene were characterized by high frequencies of the unfavorable C allele and the heterozygous T / C genotype, rs3212227 of the IL12B gene of the A allele and the heterozygous A / C genotype, rs1800895 592 C&gt; A in the IL10 gene of the A, C alleles, and heterozygous C rs5743708 in the TLR2 gene of the C allele and the heterozygous C / T genotype, hence the high level of genetic variability of the studied genes.

Prevalence of Allelic and Genotypic Variants of Il4, Il10, Il12b and Tlr2 Gene Polymorphism in Patients with Chronic Polypoid Rhinosinusitis

Chronic polyposis rhinosinusitis (CPRS) is an important medical and social problem due to its prevalence, combination with other diseases (bronchial asthma, cystic fibrosis), prolonged recurrent course, which leads to a decrease in the quality of life and performance of patients. Bronchopulmonary, rhinogenic orbital and intracranial complications arising against the background of chronic sinusitis not only worsen the quality of life of patients, but also sometimes lead to long-term disability, and sometimes to disability. The results of our study demonstrated that the distribution of the genotypes of polymorphisms of all genes corresponded to the expected, i.e., in this case, the Hardy-Weinberg equilibrium is fulfilled in both groups. Both samples rs2243250 of the IL4 gene were characterized by high frequencies of the unfavorable C allele and the heterozygous T / C genotype, rs3212227 of the IL12B gene of the A allele and the heterozygous A / C genotype, rs1800895 592 C&gt; A in the IL10 gene of the A, C alleles, and heterozygous C rs5743708 in the TLR2 gene of the C allele and the heterozygous C / T genotype, hence the high level of genetic variability of the studied genes.

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 IL-10 and TNF-α Polymorphisms with Dental Peri-Implant Disease Risk: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis.

Genetic susceptibility has been reported to be an important risk factor for peri-implant disease (PID). The aim of this meta-analysis was to assess the association between TNF-α and IL-10 polymorphisms and PID susceptibility. The Web of Science, Cochrane Library, Scopus, and PubMed/Medline databases were searched for studies published until 12 April 2021. RevMan 5.3, CMA 2.0, SPSS 22.0, and trial sequential analysis software were used. Twelve studies were included in our analysis. The pooled ORs for the association of TNF-α (−308 G > A), IL-10 (−1082 A > G), IL-10 (−819 C > T), and IL-10 (−592 A > C) polymorphisms were 1.12, 0.93, 1.35, and 0.77 for allelic; 1.42, 0.95, 3.41, and 0.34 for homozygous; 1.19, 1.88, 1.23, and 0.49 for heterozygous, 1.53, 1.12, 1.41, and 0.39 for recessive; and 1.16, 1.87, 2.65, and 0.75 for dominant models, respectively, with all the estimates being insignificant. The results showed an association between TNF-α (−308 G > A) polymorphism and the risk of PID in patients of Asian ethnicity (OR = 1.59; p = 0.03). The present meta-analysis illustrated that TNF-α (−308 G > A), IL-10 (−1082 A > G), IL-10 (−819 C > T), and IL-10 (−592 A > C) polymorphisms were not associated with the risk of PID, whereas TNF-α (−308 G > A) polymorphism was associated with an elevated risk of PID in Asian patients.

Correlation between IL-28 polymorphism and spontaneous clearance in HCV patients: systematic review and meta-analysis.

Hepatitis C virus (HCV) is a serious global health issue. Nearly 20% of HCV patients spontaneously clear the virus. While some studies have shown an association of spontaneous clearance (SC) of the virus with interleukin (IL) 28B single-nucleotide polymorphisms (SNPs), others did not show such a relationship. Thus, the purpose of the present study was to investigate the association of IL28B polymorphisms (12979860 SNP) with SC of HCV infection. Upon initial screening of the databases, a total of 545 articles were retrieved, of which 22 studies that met predefined eligibility criteria were entered into the meta-analysis. Odds ratios (ORs) with confidence intervals (95% CI), heterogeneity, publication bias, and sensitivity analysis were assessed. According to the meta-analysis results, a significant association was observed between the rs12979860 SNP and SC of HCV infection. The results indicated that the ORs of SC from hepatitis C virus infection were 2.75 times higher in those with cytokine gene polymorphisms (95% CI, 2.23 to 3.38). Moreover, it was found that the prevalence of rs12979860 CC was 0.33 with 95 CI 0.28-0.38 in genotype 1 and was 0.40 with 95 CI 0.34-0.47 in other genotypes. Our meta-analysis results suggest that IL28B rs12979860 CC is a strong predictor for SC of hepatitis C infection in PEG IFN-a/RBV-treated patients.

Association between genotypes of \(\textit{TLR4}\) gene rs2149356 polymorphism and serum level of il-6 in Vietnamese patients with gout

Gout is an inflammatory type of arthritis caused by the deposition of crystals of monosodium urate monohydrate (MSU) in the joints. The arthritis is mediated by the release of pro-inflammatory cytokines including IL-1β, TNF-α and IL-6 by leukocytes including macrophages. Toll-like receptor (TLR)4 is expressed in the immune cells to initiate immune response by inducing activation of signaling molecules involved in the transcription of nuclear genes. In this study, mutational analysis of TLR4 gene was examined to determine the prevalence of gene polymorphism in Vietnamese patients with gout. Molecular analysis of this gene was investigated by PCR amplification and direct DNA sequencing. Level of serum cytokines was measured by ELISA. As a result, no significant difference in frequency of TLR4 gene rs2149356 polymorphism was observed between the patient and control groups. Importantly, level of IL-6 was significantly higher in patients carrying CG genotype as compared with patients carrying TG and TT genotypes of TLR4 gene rs2149356 polymorphism and the patients carrying GG genotype exhibited higher IL-6 level than healthy individuals. The GG genotype of TLR4 gene rs2149356 polymorphism in gout patients were sensitive to IL6-induced inflammatory response. The effect is expected to affect the immune response to treatment for gout patients.

Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers.

Background: Previous studies have demonstrated that polymorphisms involved in immune genes can affect the risk, pathogenesis, and outcome of thoracic ascending aortic aneurysms (TAAA). Here, we explored the potential associations of five functional promoter polymorphisms in interleukin-6 (IL-6), IL-1B, IL-1A, IL-18, and Tumor necrosis factor (TNF)A genes with TAAA. Methods: 144 TAAA patients and 150 age/gender matched controls were typed using KASPar assays. Effects on telomere length and levels of TAAA related histopathological and serological markers were analyzed. Results: Significant associations with TAAA risk were obtained for IL-6 rs1800795G>C and IL-1B rs16944C>T SNPs. In addition, the combined rs1800795C/rs16944T genotype showed a synergic effect on TAAA pathogenesis and outcome. The combined rs1800795C/rs16944T genotype was significantly associated with: (a) higher serum levels of both cytokines and MMP-9 and -2; (b) a significant CD3+CD4+CD8+ CD68+CD20+ cell infiltration in aorta aneurysm tissues; (c) a significant shorter telomere length and alterations in telomerase activity. Finally, it significantly correlated with TAAA aorta tissue alterations, including elastic fragmentation, medial cell apoptosis, cystic medial changes, and MMP-9 levels. Conclusions: the combined rs1800795C/rs16944T genotype appears to modulate TAAA risk, pathogenesis, and outcome, and consequently can represent a potential predictive and prognostic TAAA biomarker for individual management, implementation of innovative treatments, and selection of the more proper surgical timing and approaches.

Association of interleukin-18 genotypes (-607C > A) and (-137 G > C) with the hepatitis B virus disease progression to hepatocellular carcinoma.

Chronic infection with HBV has been reported to be associated with the development of HCC. The inflammation mounted by cytokine-mediated immune system plays an important role in the pathogenesis of HBV-associated HCC. IL-18 is a pro-inflammatory cytokine whose role in the development of HBV-associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18, and expression level of its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR-RFLP. Genotypic distributions between the groups were compared using odd's ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression levels of pSTAT-1 and pNFƙB was determined by western blotting. In case of IL-18(- 607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(- 137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were significantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT-1 and pNF-κB) of IL-18 in stimulated PBMCs were significantly increased during HBV to HCC disease progression. These findings suggest that IL-18 has the potential to act as a biomarker of HBV-related disease progression to HCC.

Dietary Acid Load and Its Interaction with IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) Polymorphisms on Metabolic Traits among Postmenopausal Women.

The objective of this study was to explore the effects of dietary acid load (DAL) and IGF1 and IL6 gene polymorphisms and their potential diet–gene interactions on metabolic traits. A total of 211 community-dwelling postmenopausal women were recruited. DAL was estimated using potential renal acid load (PRAL). Blood was drawn for biochemical parameters and DNA was extracted and Agena® MassARRAY was used for genotyping analysis to identify the signalling of IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) polymorphisms. Interactions between diet and genetic polymorphisms were assessed using regression analysis. The result showed that DAL was positively associated with fasting blood glucose (FBG) (β = 0.147, p < 0.05) and there was significant interaction effect between DAL and IL6 with systolic blood pressure (SBP) (β = 0.19, p = 0.041). In conclusion, these findings did not support the interaction effects between DAL and IGF1 and IL6 single nucleotide polymorphisms (rs35767, rs7136446, and rs1800796) on metabolic traits, except for SBP. Besides, higher DAL was associated with higher FBG, allowing us to postulate that high DAL is a potential risk factor for diabetes.

Contributing role of TNF, IL-10, sTNFR1 and TNF gene polymorphisms in disease severity of leptospirosis.

The immune response is hypothesized as an important factor in the disease outcome of leptospirosis. Exaggerated immune response may promote tissue damage that lead to severe disease outcome. In this study TNF, IL-10, sTNFR1 levels were measured among sixty-two hospitalized leptospirosis confirmed patients in Sri Lanka. Thirty-one serum samples from healthy individuals were obtained as controls. PCR–RFLP method was used to identify TNF gene polymorphisms and to determine their association with TNF expression and disease severity in leptospirosis. TNF (p = 0.0022) and IL-10 (p < 0.0001) were found to be significantly elevated in leptospirosis patients, while sTNFR1 (p < 0.0001) was significantly suppressed. TNF was not significantly elevated in patients with complications while the anti-inflammatory cytokine IL-10 was significantly elevated among patients with complications (p = 0.0011) and with mortality (p = 0.0088). The ratio of IL-10 to TNF was higher among patients with complications (p = 0.0008) and in fatal cases (p = 0.0179). No association between TNF gene polymorphisms and TNF expression was detected due to the low frequency of heterozygous and mutated genes present in this study population. Thus the findings of the study show that elevated levels of IL-10 in the acute phase of disease could lead to severe outcomes and a high IL-10/TNF ratio is observed in patients with complications due to leptospirosis.