Interleukin-6 Genotypes Research Articles

Interleukin-6 gene polymorphisms and susceptibility to liver diseases

Background:Several studies have explored the associations between interleukin-6 (IL-6) gene polymorphisms and the susceptibility to liver diseases, however, results remain ambiguous. The goal of this study was to conduct a meta-analysis to provide more credible evidence.Methods:Studies identified in the PubMed, Cochrane Library, and EMBASE databases were used to perform a meta-analysis via the STATA software. Pooled odds ratios (OR) were calculated under fixed- and random-effects models to estimate the potential genetic associations.Results:Twenty-five case-control studies involving 5813 cases and 5298 controls were included in this meta-analysis. Overall, the pooled results suggested that rs1800795 polymorphism was significantly associated with the risk of liver diseases in heterozygote (GC vs CC; OR = 1.57) and dominant (GG+GC vs CC: OR = 1.47) models; rs1800796 polymorphism was significantly associated with the susceptibility to liver diseases in heterozygote (GG vs GC; OR = 0.58) and recessive (GG vs GC+CC: OR = 0.68) models; rs1800797 polymorphism was significantly associated with genetic predisposition to liver diseases in homozygote (GG vs AA: OR = 1.63), heterozygote (GA vs AA; OR = 1.53) and dominant (GG + GA vs AA: OR = 1.61) models. A similar conclusion was found in the HBV, HCV, HCC, NASH and alcoholic liver disease of all ethnic populations for rs1800795; HBV and Asian subgroups for rs1800796; HCV and non-Asian subgroups for rs1800797. However, IL-6 rs2069837 and rs2066992 polymorphisms did not exhibit significant associations with the risk of liver diseases under any genetic models.Conclusion:This meta-analysis suggests that patients carrying G (rs1800795), C (rs1800796) or G (rs1800797) allele or genotypes of IL-6 may be more likely to suffer from liver diseases, which was ethnic-dependent.

Interactions Between Diet Quality and Interleukin-6 Genotypes Are Associated With Metabolic and Renal Function Parameters in Mexican Patients With Type 2 Diabetes Mellitus

The aim of this study was to evaluate the interaction between diet quality and interleukin (IL)-6 genotypes and its association with metabolic and renal function parameters in Mexican patients with type 2 diabetes mellitus (T2DM). Using an analytical cross-sectional design, 219 patients with T2DM (92 men; age 62±10years) were evaluated for selected metabolic and renal function parameters. Diet quality according to the Healthy Eating Index was evaluated and classified as good diet or poor diet in all patients. IL-6 serum concentrations and genotypes and haplotypes for IL6-597G>A (rs180097), -572G>C (rs180096), and -174G>C (rs180095) polymorphisms were determined. Eighty-two percent of patients reported having a poor diet. Carriers of alleles -572C and -174C showed higher high-density lipoprotein cholesterol levels (44±12 vs. 40±9mg/dL; P = .01) and lower total cholesterol levels (184±33 vs. 197±42mg/dL; P=.03) than did those homozygous for G/G. Neither IL6 genotypes nor haplotypes were significantly associated with serum concentrations of IL-6. Some significant interactions between IL6 genotypes/haplotypes and diet quality were associated with body mass index, waist circumference, high-density lipoprotein cholesterol levels, and estimated glomerular filtration rate. Interactions between diet quality and IL6 genotypes/haplotypes were associated with the main metabolic and renal function parameters in Mexican patients with T2DM. It will be important to consider genetic profiles in designing dietary portfolios and nutritional interventions for the management of such patients.

Identification of Periopathogenes from Dental Plaque in Periodontal Patients with PCR Technique and Their Association with Composite Interleukin-1 Genotype.

The present study aimed to assess the presence of main types of microorganisms involved in the aetiopathogenesis of chronic periodontitis with PCR technique and determinates the presence of composite IL-1 genotype and their associations with founded bacteria. The examined group was consisted from 20 subjects with diagnosed chronic periodontitis and 20 healthy control without periodontitis. Clinical parameters like gingival index (GI), plaque index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD) and clinical attachment lost (CAL) were determinates. Subgingival dental plaque was collected using a sterilized paper point. We used Parodontose Plus test, reverse hybridization kit, for the detection of periodontal marker bacteria, as well as for the detection of composite Interleukin -1 Genotype Results: The most present bacterial species detected from subgingival dental plaque was Treponema denticola and Porfiromonas gingivalis which was present in 65% of examined patients. In relation to the presence of positive genotype in patients, there was no significant difference between the test and control group for p> 0.05 (p = 1.00). For χ2=8,17 (p=0,06, p<0,05) there is an association between Prevotella intermedia, and composite genotype. Between positive genotype and analyzed bacterial species A. actinomycetem comitans for p> 0.05 (p = 1.00), P. gingivalis for p> 0.05 (p = 0.16), T. Forsythia for p> 0.05 (p = 0.20), T. Denticola for p> 0.05 (p = 0.64) no association was found. This investigations confirmed the strong association of these five examined periopathogenes with periodontitis.

The Effect of Habitual Fat Intake, IL6 Polymorphism, and Different Diet Strategies on Inflammation in Postmenopausal Women with Central Obesity.

The hypothesis that habitual fat intake, the IL6 genotype, the Mediterranean diet or the central European diet for 16 weeks affect biomarkers of inflammation in centrally obese postmenopausal women, was tested in a randomized controlled trial. Dietary intake was assessed using a three-day food diary. Lipid parameters were measured using a Beckman Coulter AU analyzer. Transcription of TNF and IL6 genes was analyzed in peripheral blood mononuclear cells using real-time PCR. Concentrations of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6) were measured with ELISA. rs1800795 polymorphism of IL6 was analyzed using hydrolyzing probes. Higher energy intake from fat was associated with higher IL6 levels (p < 0.05). Significantly (p < 0.01) lower total cholesterol (T-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were observed in the GG IL6 rs1800795 genotype group. Both diets significantly (p < 0.001) decreased TNFα concentrations. Neither IL6 gene transcription levels nor blood IL6 concentrations were affected by them. Our findings confirm that habitual fat intake may affect inflammation. The rs1800795 IL6 polymorphism alone did not significantly affect body weight or body composition in aimed group, but C-allele carriers had higher levels of T-C and LDL-C. This polymorphism did not affect inflammation. Both diets may lead to a decrease in TNFα concentration.

Correlation between interleukin-6 single nucleotide polymorphism and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure

Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion: The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.

Association of Interleukin-10 Genotypes and Oral Cancer Susceptibility in Selected Malaysian Population: A Case- Control Study

Background:Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10 A1082G gene polymorphism was correlated.Methodology:41 oral squamous cell carcinoma (OSCC) cases and 48 healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square test and Fisher’s Exact test were used in statistical analysis.Results:AG genotypes were present in 81.3% and 86.0% of healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival. The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion.Conclusion:This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence to support the lack of association of IL10 A1082G polymorphism in oral cancer.

Study of the effect of interleukin-6 gene polymorphism in patients with rheumatoid arthritis

Background Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. Although the clear etiology of RA remains to be elucidated, it is widely accepted that RA is a complex disease, and both environmental and genetic factors can contribute to disease initiation as well as its evolution. The −174G/C polymorphism of interleukin-6 (IL-6) gene has been reported to be responsible for changes in the expression of IL-6, which could in turn lead to greater inflammation and thus affect the clinical status of patients with RA. Aim To determine the association of IL-6 gene polymorphism with patients with RA by studying the frequency of the polymorphism of IL-6 (−174G/C) gene in those patients compared with healthy participants to predict the risk of development of RA. Patients and methods The study was conducted on 200 (150 patients with RA and 50 age-matched and sex-matched healthy control) adult Egyptian patients. IL-6 (−174G/C) genotypes were determined by PCR-restriction fragment length polymorphism analysis. Results The prevalence of polymorphic genotype of GC and CC and C allele was statistically significantly increased in patients with RA than in control (P Conclusion The GC and CC genotype and C allele of IL-6 (−174G/C) may represent a significant genetic molecular marker to predict the risk of RA.

DYNAMICS OF INDICATORS OF LIPID AND CYTOKIN PROFILES, SYSTEM OF OXIDANT AND ANTIOXIDANT PROTECTION IN PATIENTS WITH OSTEOARTHRITIS IN COMBINATION WITH ARTERIAL HYPERTENSION, OBESITY AND TYPE 2 DIABETES CONSIDERING GENOTYPES OF INTERLEUKIN 10 (IL-10, C-592

Purpose. To study the dynamics of indicators of lipid and cytokine profiles, system of oxidant and antioxidant protection in patients with osteoarthritis in combination with arterial hypertension, obesity and type 2 diabetes considering genotypes of interleukin 10 (IL-10, C-592a) under the influence of treatment.Material and methods. The stage of screening was passed through by 74 patients with OA, AH and D 2 and 25 practically healthy individuals. Polymorphism IL-10 (C-592A) was determined by polymerase chain reaction, and when evaluating the effectiveness of treatment, the presence of comorbid pathology was taken into account.Results. Under the influence of treatment, the content of total cholesterol and LDL cholesterol after treatment significantly decreased in all patients with genotypes IL-10 gene (C-592A), with the possible intergroup difference in the indices with carriers of AA and CA-genotype IL-10 (C-592A). It was found that the TG (triacylglycerols) content among the carriers of the AA-genotype after treatment was the highest: so in comparison with carriers of the СС-genotype - by 29,3% (pCC=0,029) and 43,9% compared with carriers of the CA-genotype (p=0,006). The content of LDL cholesterol significantly decreased in the presence of the CC-genotype by 1.27 times (p=0.003) and the AA-genotype - about twice (p=0.0002), with the possible intergroup difference between the AA and CC-genotype carriers (pCC=0.0001) and the CA-genotype (pCA=0.001) IL-10 (C-592A). In patients with the AA-genotype after the application of complex treatment prescribing atorvastatin, the index of atherogenicity decreased significantly (1.66 times, p=0.002).The probable decrease in the activity of oxidative stress indicators was established (more effective in carriers of the C-allele of the IL-10 gene (C-592A)) against a background of an unlikely increase in antioxidant defense that did not depend on polymorphous variants of the IL-10 gene (rs1800872). The concentration of proinflammatory cytokine IL-18 in patients with osteoarthrosis decreased by 25.6% in the CC-genotype carriers, by 18.58% in the CA-genotype, by 15.37% in the AA-genotype (p&gt;0.05). The content of anti-inflammatory IL-10, on the contrary, increased by 11.69%, 18.0% and 23.08% (p&gt;0.05), respectively. Under the influence of treatment, an insignificant increase in the extracellular matrix protein matriline 3 was observed: in the carriers of the CC-genotype by 4.4%, in the CA-genotype - by 13.5%, and in the AA genotype - by 13.8% (p&gt;0.05).Conclusions. After the treatment, the improvement of lipid profiles in the AA-genotype carriers was the most significant.

Interleukin 6 and 10 Serum Levels and Genetic Polymorphisms in Children with Down Syndrome.

Immunological impairment is a condition that is often observed in individuals with Down syndrome (DS). The immune response is modulated by pro- and anti-inflammatory cytokines whose expressions could be influenced by genetic polymorphisms. The present study was aimed at evaluating the frequencies of -174G>C, -572G>C, and -597G>A polymorphisms in the interleukin 6 (IL-6) gene and -592C>A, -1082A>G, and -819C>T polymorphisms in the IL-10 gene and the IL-6 and IL-10 serum levels in healthy individuals with and without DS. The authors also aimed to investigate the impact of the genotypes on the interleukin concentrations. The genetic polymorphisms were investigated in 200 DS individuals and 200 controls without DS. The serum measurement of IL-6 and IL-10 was performed in a subgroup (54 cases and 54 controls) by enzyme-linked immunosorbent assay (ELISA). The frequencies of the polymorphisms and haplotypes evaluated were not different between individuals with and without DS. IL-10 concentration was higher in DS children but was not influenced by IL-10 gene polymorphisms. IL-6 genotypes had no influence on IL-6 serum levels. The IL-10 serum levels are increased in DS individuals, but IL-10 polymorphisms are not the main factors that influence the IL-10 expression in DS.

Association between the -174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis

Genetic predisposition to systemic sclerosis (SSc) has still not been fully revealed. Interleukin-6 (IL-6) is a mediator of T cell proliferation and fibrotic events in SSc. Polymorphisms in the IL-6 are found to be important in susceptibility to development of SSc. We aimed to assess the frequency of -174 C/G of IL-6 gene polymorphism in SSc patients and healthy controls, as well as correlation with disease manifestations. In the case-control study, 102 patients with SSc and 93 controls were included. PCR-RFLP method was performed for genotyping promotor variants -174 C/G of IL-6 gene. The expression level of IL-6 was determined by qRT-PCR on subset of 50 patients and 13 healthy controls with different IL-6 genotypes. We used UCLA GIT 2.0 questionnaire to assess gastrointestinal involvement in SSc patients. The expression level of IL-6 gene was significantly higher in patients with SSc in comparison with healthy controls (p < 0.05). Carriers of C-allele of IL-6 gene compared to those with G allele, showed higher expression of IL-6 gene (95.8 vs. 41.2, p < 0.05), higher GIT total score (0.85 vs. 0.5, p < 0.05) and higher distension scale score (1.4 ± 0.9 vs. 0.78 ± 0.8, p = 0.05). No significant differences in genotype distribution and allele frequency were observed between patients and controls. The expression of IL6 gene varies significantly during the course of SSc. The IL-6 gene variant -174 C/G (presence of C-allele) is associated with higher IL-6 gene expression and greater GIT impairment in patients with SSc.

Association of interleukin-6 (rs1800796) but not transforming growth factor beta 1 (rs1800469) with serum calcium levels in osteoporotic patients

BackgroundOsteoporosis is a multifactorial disease with a strong genetic influence. Recent studies have demonstrated that cytokines, such as TGF-β1 and interleukin 6 (IL-6) play complex roles in the normal bone metabolism and pathophysiology of osteoporosis. Here, we investigated the roles of 2 polymorphisms mapping to the promoters of TGF-β1and IL-6 genes on the genetic susceptibility to osteoporosis as well as calcium and vitamin D levels. MethodsA cohort of 297 elderly participants in northern Iran comprising 181 osteoporotic patients (mean age ± SD, 68.36 ± 7.21 years) and 116 unrelated healthy controls (mean age ± SD, 64 ± 5.44 years) was studied for TGF-β1(C-509T) and IL-6 (G-634C) polymorphisms using PCR-RFLP method. ResultsA significant relationship was observed between calcium level and IL-6 genotypes in osteoporotic males (P = 0.011) and females (P = 0.020). No significant differences were observed between osteoporotic and control groups with respect to allele frequency or genotype distribution based on the 2 selected polymorphisms under different genetic models. The results remained the same after comparing the BMD values of either the femur neck or lumbar spine with the genotypes of the elderly men and women when analyzed separately. ConclusionIL-6 genotype influences serum calcium levels in osteoporotic patients. The lack of association between the common genetic variations of TGF-β1 and IL-6 genes, and BMD highlights the complex genetic background of osteoporosis in the north of Iran.

Identification of Functional Genetic Polymorphisms at IL-10 Promoter Region and their Association with Risk of Ischemic Stroke in Chinese Han Population.

Pleiotropic cytokine interleukin-10 (IL-10) has been suggested as modifying risk for atherosclerosis. Promoter region genetic polymorphism of IL-10 gene is known to be associated with the level of IL-10 production. Through these effects, they might be involved with the ischemic stroke (IS). Our aim was to assess the nature of the functional polymorphisms in IL-10 promoter and any links with IS in Chinese Han population. The IL-10 -1082 G>A, -819 C>T and -592 C>A functional polymorphisms were determined by TaqMan SNP Genotyping assays in 1296 subjects (648 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 648 normal healthy controls from Chinese Han Population). Multivariate logistic regression analysis was used to show the association between the IL-10 genotypes and the IS events. We found that the CC genotype of -819 C>T was more common in controls than IS subjects (P<0.05, corrected for multiple testing) in the Han population. CC carriage may be associated with the decreased risk of IS in the Han ethnic group (OR 0.65, 95% CI 0.43-0.97). In addition, the CC genotype in -592 C>A and GG genotype in -1082 G>A are all extremely low in Chinese Han cases and controls. The G allele frequency at the -1082 promoter region of IL-10 was rare in Chinese Han population which are diffierent from American/European populations.. IL-10 -819 C>T may be an independent protective factor for IS in the Chinese Han population.

The effects of IL-10 gene polymorphism on serum, and gingival crevicular fluid levels of IL-6 and IL-10 in chronic periodontitis.

ObjectiveAnti-inflammatory cytokines play a crucial role in periodontitis by inhibiting synthesis of pro-inflammatory cytokines. The purpose of this study was to evaluate the effect of interleukin-10 (-597) gene polymorphism and genotype distributions on chronic periodontitis (CP) development and IL-6 and IL-10 levels in gingival crevicular fluid (GCF) and serum before and after non-surgical periodontal treatment.Material and MethodsThe study population consisted of 55 severe generalized CP patients as CP group and 50 healthy individuals as control group. Plaque index, gingival index, probing depth and clinical attachment level were recorded and GCF and blood samples were taken at both the baseline and the sixth week after non-surgical periodontal treatment. PCR-RFLP procedure was used for gene analyses and cytokine levels were measured via ELISA.ResultsIL-10 genotype distribution was significantly different between CP and control groups (p=0.000, OR:7, 95%CI, 2.83-60.25). Clinical measurements significantly improved in the CP group after periodontal treatment (p<0.05). Periodontal treatment significantly decreased GCF IL-6 and IL-10 levels. No significant difference was found in clinical parameters between IL-10 AA and AC+CC genotypes at both the baseline and the sixth week (p>0.05). Sixth week GCF IL-10 levels were significantly lower in patients carrying IL-10 AC+CC genotype compared to the patients carrying IL-10 AA genotype (p<0.05). Serum IL-6 and IL-10 levels were lower in patients carrying the IL-10 AA genotype compared to patients with IL-10 AC+CC genotype, but the difference was not significant (p>0.05).ConclusionIL-10 AA genotype carriers had lower IL-6 and IL-6/10 levels in serum; however, GCF IL-6/10 levels were similar in both genotypes. Within the limitations of our study, a possible association between IL-10(-597) gene polymorphism and CP might be considered.

Interleukin-6 gene polymorphisms and serum erythropoietin and hemoglobin in hemodialysis Iraqi patients.

Chronic kidney disease (CKD) is characterized by elevated levels of pro-inflammatory cytokines. Interleukin-6 (IL-6) is a pleiotropic and pro-inflammatory cytokine involved in different biological activities such as hematopoiesis, inflammation, and acute-phase response. The rate of IL-6 synthesis and degradation is affected by single nucleotide polymorphisms. This study aimed to evaluate the frequencies of 174G/C IL-6 gene promoter polymorphism in Iraqi hemodialysis (HD) patient and to examine the association between the allelic variations and serum erythropoietin (EPO) and hemoglobin (Hb) levels. The frequencies of IL-6 gene polymorphism were studied in 70 chronic renal failure patients on maintenance HD (patients group) and in 20 healthy participants (control group). Genotyping of IL-6 gene was performed by conventional polymerase chain reaction-restriction fragment length polymorphism. The distribution of IL-6 genotypes between groups was similar, and GG genotype is the most frequent followed by CG and CC genotypes. Control group had a nonsignificant difference in serum EPO levels among different IL-6 genotypes, while patients with GG genotype displayed significant elevation in serum EPO with time, followed by CG and CC genotypes. No significant differences in Hb levels were observed in patients and control groups. A significant positive correlation was observed between serum EPO and Hb in control group with different IL-6 genotypes, while a nonsignificant negative correlation was observed in patients group throughout the study. CKD did not significantly alter IL-6 genotypes, and IL-6 gene polymorphism had a significant effect on serum EPO levels and a nonsignificant effect on Hb levels.

Association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism with vitiligo susceptibility in Gujarat population.

Vitiligo is a multifactorial, polygenic, autoimmune skin disorder caused by selective destruction of melanocytes. Interleukin 1 receptor antagonist intron 2 polymorphism was found to be associated with various autoimmune disorders. We aimed to investigate the association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism (rs2234663) with vitiligo to assess interleukin 1 receptor antagonist transcript levels and to perform possible genotype-phenotype correlation. Three hundred and seven vitiligo patients and 316 controls were enrolled in the study, genotyping of interleukin 1 receptor antagonist rs2234663 was performed by polymerase chain reaction, and relative gene expression of interleukin 1 receptor antagonist was carried out in peripheral blood mononuclear cells from patients (n = 36) and controls (n = 36) by real-time-PCR. A significant difference was observed in the frequency of interleukin 1 receptor antagonist *A (1/2) genotype among patients with active and stable vitiligo (P = 0.0172). Interleukin 1 receptor antagonist*A (2/2) genotype and allele frequencies were significantly different between SV patients and controls (P = 0.0246 and P = 0.0046, respectively). Significant difference was also observed for interleukin 1 receptor antagonist*A2 (allele) in active and stable vitiligo patients (P = 0.0060). However, other comparisons did not show any significant difference in genotype and allele frequencies. Moreover, interleukin 1 receptor antagonist*A (3/2) genotype was observed only in patients whereas interleukin 1 receptor antagonist*A (5/2) was observed only in controls. Gene expression analysis showed no significant difference in interleukin 1 receptor antagonist transcript levels in patients compared to controls (P = 0.5962). Interestingly, genotype-phenotype correlation analysis revealed that individuals with IL1RN*A (2/2) exhibited higher interleukin 1 receptor antagonist expression compared to other major genotypes interleukin 1 receptor antagonist*A (1/2) (P = 0.01) and interleukin 1 receptor antagonist*A (1/1) (P = 0.03). More case-control studies on interleukin 1 receptor antagonist rs2234663 polymorphism and gene expression from different ethnic populations are required to explore the impact of interleukin 1 receptor antagonist in vitiligo susceptibility. Interleukin 1 receptor antagonist*A2 might be a risk factor for progressive vitiligo.

Coexistence of IL-6 -572C/G and ICAM-1 K469E Polymorphisms among Patients with Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSNHL) is a multifactorial disease, and its etiology remains elusive. SSNHL is possibly caused by both the environmental factors and genetic alterations. Recently, several studies suggested that inflammation may be involved in the pathogenesis of SSNHL, and certain gene polymorphisms may have correlations with SSNHL. Interleukin 6 (IL-6) functions both as a pro-inflammatory cytokine and an anti-inflammatory factor. Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin family that is also involved in inflammation response. Importantly, the IL-6 gene promoter contains a single nucleotide polymorphism (SNP), -572C/G, and ICAM-1 gene contains a SNP (A/G) in the protein-coding region, Lys (AAG)/Glu (GAG) at codon 469, known as K469E polymorphism. However, there is no study about the ICAM-1 gene polymorphism among SSNHL patients. In this study, we explored the relationship between SSNHL with IL-6 -572C/G and ICAM-1 K469E polymorphisms. We conducted a case-control study including 75 SSNHL patients and 165 healthy controls and analyzed the distribution and odds ratios of IL-6 and ICAM-1 genotypes. The frequency of the G allele at IL-6 -572C/G polymorphism was significantly higher among SSNHL patients than that among healthy individuals. In multivariate analysis, the coexistence of IL-6 -572G allele (GG/CG) and E allele (EE/KE) of ICAM-1 K469E polymorphism was significantly associated with an increased SSNHL risk (P < 0.001). In conclusion, we propose that the combination of IL-6 -572C/G and ICAM-1 K469E polymorphisms have a synergistic effect on the onset of SSNHL.

Interleukin-1 genotypes modulate the long-term effect of lipoprotein(a) on cardiovascular events: The Ioannina Study

Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease (CVD), and proinflammatory interleukin-1 (IL-1) genotypes may influence Lp(a)-mediated CVD events. The genotype IL-1(+) is associated with higher rates of inflammation than IL-1(-) genotype. Targeting IL-1β was recently shown to decrease CVD events independent of low-density lipoprotein-cholesterol levels. The objective of the study is to assess the modulatory effect of IL-1 genotypes on risk mediated by Lp(a) METHODS: We assessed whether IL-1 genotypes modulate the effect of Lp(a) on major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke/transient ischemic attack) and angiographically determined coronary artery disease (CAD). IL-1 genotypes and Lp(a) were measured in 603 patients without diabetes mellitus undergoing angiography. Major adverse cardiovascular events and CAD were assessed over a median of 45months. In multivariable-adjusted analysis, Lp(a) was associated with major adverse cardiovascular events (hazard ratio [HR] [95% confidence interval {CI}]: 2.95 [1.16-7.54], P=.023) and CAD (odds ratio [OR] [95% CI]: 1.84[1.12-3.03], P=.016) comparing quartile 4 vs quartile 1. In Cox regression analysis, IL-1(+) patients with Lp(a) above the median (>9.2mg/dL) had a worse event-free cumulative survival (HR [95% CI]: 3.59 [1.07-12.03], P=.039) compared to IL-1(-) patients with Lp(a) below the median. In IL-1(+) patients aged ≤60years, Lp(a) was also associated with angiographically determined CAD (OR [95% CI]: 2.90 [1.07-7.86], P=.036) comparing quartile 4 vs quartile 1 but not IL-1(-) patients. Proinflammatory IL-1(+) genotypes modulate the risk of Lp(a) long-term CVD events and CAD. These data suggest that the dual genetic contributions of elevated Lp(a) levels and IL-1(+) genotypes may identify younger subjects at particularly high risk for CVD events.

Cytokines Interleukin 4 (IL-4) and Interleukin 10 (IL-10) Gene Polymorphisms as Potential Host Susceptibility Factors in Virus-Induced Encephalitis.

BackgroundThis study aimed to analyze and explore the relationship between the cytokines IL-4 and IL-10 in relation to gene polymorphism and their respective effects on the susceptibility to virus-induced encephalitis.Material/MethodsFrom January 2012 to June 2013, 112 patients with virus-induced encephalitis (the case group and 109 healthy individuals (the control group) were recruited for the purposes of this study. The functional variations that IL-4 and IL-10 genes exhibit were detected through the use of a function analysis and selection tool for single-nucleotide polymorphisms (FASTSNP). The genotypes of IL-4 were rs2227283 and IL-4 rs2227288, and the genotypes of IL-10 were rs1800871 and IL-10 rs1800872. These genotypes were respectively assessed using direct sequencing.ResultsIL-4 rs2227283 and IL-10 rs1800871 have no correlation in with risk of virus-induced encephalitis (both P>0.05)GA and AA genotypes were related to IL-4 rs2227288 and GT, while TT and GT + TT genotypes were related to IL-10 rs1800872. These were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). However, the duration of fever, white blood cell (WBC) count, C-reactive protein (CRP), neutrophils, and lymphocytes and monocytes of virus-induced encephalitis patients with IL-4 rs2227288 and IL-10 rs1800872 all displayed significant differences (all P<0.05). Frequencies of GAGT and CAGT haplotypes were evaluated and deemed to be of statistical significance and subsequently were highlighted as being risk factors in virus-induced encephalitis (all P<0.05).ConclusionsIL-4 rs2227288 and IL-10 rs1800872 may contribute to an increased risk for virus-induced encephalitis. Through use of direct sequencing, we showed that genotypes of IL-4 rs2227288 and IL-10 rs1800872 may have particular host susceptibility to virus-induced encephalitis.

P1768Impact of inflammatory interleukin-1 genotypes on risk of infection in UK Biobank

P1768Impact of inflammatory interleukin-1 genotypes on risk of infection in UK Biobank

P1761Diabetic status influences the effect of pro-inflammatory interleukin-1 genotypes on lipoprotein(a) mediated risk of coronary artery disease and cardiovascular events

P1761Diabetic status influences the effect of pro-inflammatory interleukin-1 genotypes on lipoprotein(a) mediated risk of coronary artery disease and cardiovascular events