Interleukin-6 Genotypes Research Articles

Potential influence of interleukin-6 -174G/C gene polymorphism on kidney graft function and tacrolimus dose requirements: five-year follow-up

1. Introduction The study aimed to investigate the influence of interleukin (IL)-6 -174 G/C gene polymorphism on graft function (defined as estimated glomerular filtration rate, eGFR), as well as on the tacrolimus (Tac) pharmacokinetics during the five years after kidney transplantation. 2. Methods The study included 115 Caucasian kidney transplant recipients on Tac-based immunosuppression. The patients were followed between 6 and 60 post-transplantation months. Interleukin-6 and CYP3A5 genotyping were performed. 3. Results Patients carrying the IL-6 -174GG genotype had lower eGFR values compared to the patients with the IL-6 -174GC and −174CC genotypes at the 12th, 48th and 60th post-transplantation months. The linear regression analysis indicated that eGFR at the 6th post-transplantation month and IL-6 -174 G/C polymorphism are independent predictors of eGFR values in the late post-transplantation period. The IL-6 -174GG genotype carriers had lower dose-adjusted trough concentration (C0/D) of Tac compared to the IL-6 C allele carriers during the entire observation period (except at the 24th month), while this effect was independent of the CYP3A5 genotype within three years post-transplantation. 4. Conclusion Interleukin-6 genotyping could be an additional tool to categorise patients towards the risk of graft deterioration in the long-term post-transplantation period. The IL-6 genotyping could be supportive in genotype-guided dosing of Tac.

Short Physical Performance Battery (SPPB) and Its Relationship with the Predisposition to Muscle and Joint Injuries Associated with the COL1A1 and IL-6 Gene in Older Adults.

Background/Objectives: Aging leads to physiological changes influenced by lifestyle, environment, and genetics, increasing the risk of morbidity and mortality in older adults. COL1A1 gene encodes an essential protein in connective tissues, which is associated with musculoskeletal lesions. The interleukin-6 (IL-6) gene is a proinflammatory and anti-inflammatory regulator and has a greater predisposition to fractures and osteoporosis reported. In turn, these alterations are associated with a decrease in physical capacity, leading to a progressive loss of functionality and quality of life in older adults. Methods: A cross-sectional study was designed to identify the relationship between physical condition as determined using the Short Physical Performance Battery (SPPB) and the predisposition parameters for muscle and joint injuries in a population of 422 older adults, active and of ≥60 years. The variables evaluated were sociodemographic data, SPPB evaluation, and COL1A1 and IL-6 gene DNA extracted by buccal scraping. Results: SPPB total score was significantly correlated with age -0.07, weight -0.02, waist circumference -0.02, and body mass index -0.05 (p < 0.005). Conclusions: Regarding genetic variables, there were no significant differences. However, lower SPPB values were observed in the GG genotype and GT of COL1A1 when compared to the CC genotype and GC of IL-6.

Clinical Significance of IL-6 Gene Polymorphism on Erythropoietin Responsiveness in Hemodialysis Patients

Abstract Background The plasma levels of the cytokine interleukin-6 (IL-6) have been reported to be associated with risk of chronic kidney disease (CKD) and erythropoietin (EPO) responsiveness. The G/C promoter polymorphism of IL-6 is associated with expression and levels of IL-6, so it may confer increased risk to CKD and modulate EPO responsiveness. Aim of the Work This study aims to evaluate the frequency of 174G/C IL-6 gene promoter polymorphism in hemodialysis (HD) patients and to assess the impact of this allelic variation on erythropoietin (EPO) responsiveness. Patients and Methods This study was conducted on fifty Chronic Kidney Disease (CKD) patients undergoing hemodialysis (HD) recruited from Nephrology Medicine Department at Ain Shams University hospitals, and ten healthy age and sex matched controls. All patients received recombinant human erythropoeitin (rHu-Epo) regimens for treatment of anemia. All the patients were subjected to full history taking, basic laboratory investigations (CBC, Iron profile and kidney function tests) as well as determination of IL-6 rs1800795 (-174 G/C) gene polymorphism using Real time-polymerase chain reaction technique (RT-PCR). The patient’s group was further classified into two subgroups according to Hb level in response to erythropoietin stimulating agents (ESAs) in accordance with the European Best Practice Guidelines, in which responders have a Hb level ≥11 g/dl, and ESA non-responders have a Hb level&amp;lt;11 g/dl. The Erythropoietin resistance index (ERI) was calculated for all patients, with a median (IQR) of 16.5 (14.31 - 19.96). Accordingly all patients were further classified into tertiles according to the ERI. The higher tertile group is classified as more hypo-responsive/resistant. Results In the present study, The IL-6 -174 G/G genotype was the most common among the cases group. Seventy four percent of the patients had the wild GG genotype and 24% had heterozygous GC genotype while only 2% had the homozygous CC genotype. In the control group the G/G genotype was detected in (80%) of subjects followed by G/C genotype (20%). No statistically significant difference was observed between the control and cases group regarding the IL-6 genotype frequencies. Only eight out of fifty (16%) patients reached the target Hb, 4 of them (50%) had the GG genotype and the other 4 (50%) had the GC genotype. The non-responders genotypes were distributed as 78.6% GG genotype, 19% GC genotype and 2.4% with CC genotype. There was no statistical significant difference regarding the genotype frequencies of IL-6 gene polymorphism between the two groups. Similarly no statistically significant association was found between the IL-6 gene genotypes and the ERI tertiles. Conclusion IL-6 -174 G/C gene polymorphism was not found to be associated with EPO hypo-responsiveness in CKD patients in the studied group nor with the increased Erythropoeitin resistance index (ERI) values among them.

Impacts of Interleukin-10 Promoter Genotypes on Prostate Cancer.

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 (IL-10) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa (p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28-11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05-3.45 and 2.30-17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)-Associated Cardiovascular Risk.

Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is heavily influenced by genetic factors, including LPA kringle IV-2 domain size, single-nucleotide polymorphisms, and interleukin-1 genotypes. Apolipoprotein(a) is encoded by the LPA gene and contains 10 subtypes with a variable number of copies of kringle -2, resulting in >40 different apolipoprotein(a) isoform sizes. Genetic loci beyond LPA, such as APOE and APOH, have been shown to impact lipoprotein(a) levels. Lipoprotein(a) concentrations are generally 5% to 10% higher in women than men, and there is up to a 3-fold difference in median lipoprotein(a) concentrations between racial and ethnic populations. Nongenetic factors, including menopause, diet, and renal function, may also impact lipoprotein(a) concentration. Lipoprotein(a) levels are also influenced by inflammation since the LPA promoter contains an interleukin-6 response element; interleukin-6 released during the inflammatory response results in transient increases in plasma lipoprotein(a) levels. Screening can identify elevated lipoprotein(a) levels and facilitate intensive risk factor management. Several investigational, RNA-targeted agents have shown promising lipoprotein(a)-lowering effects in clinical studies, and large-scale lipoprotein(a) testing will be fundamental to identifying eligible patients should these agents become available. Lipoprotein(a) testing requires routine, nonfasting blood draws, making it convenient for patients. Herein, we discuss the genetic determinants of lipoprotein(a) levels, explore the pathophysiological mechanisms underlying the association between lipoprotein(a) and cardiovascular disease, and provide practical guidance for lipoprotein(a) testing.

POLYMORPHISMS IN THE ACE2 AND IL-6 GENES AND THEIR POTENTIAL IMPACT ON THE SUSCEPTIBILITY OF SEVERE COVID-19 AMONG ERBIL HOSPITALIZED PATIENTS

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a transmissible illness caused worldwide pandemic. This virus invades host cells via receptors of angiotensin-converting enzyme 2 (ACE2). Moreover, the viral infection stimulates the production of a variety of cytokines like interleukin-6 (IL-6). The main aim of this work is to investigate the connection between COVID-19 and polymorphism of ACE2 (rs2106809 and rs2285666) and IL-6 (-174 G/C) (rs1800795) genes in a group of patients. Genomic DNA was prepared from the peripheral blood of 60 hospitalized patients and 22 controls, the ACE2 and IL-6 genes were amplified by PCR, and the products were sequenced. The data demonstrated a significant variation in the genotype frequency of ACE2 between COVID-19 patients and healthy subjects.The ACE2 (rs2106809) polymorphism outcomes expressed the frequency of three genotypes (TT, TC, and CC), the patients with the TC allele are at risk of developing the disease by approximately 8-folds (OR= 7.5) compared to those with TT and CC alleles. Furthermore, no significant association was found between ACE2 (rs2285666) polymorphism and the risk of developing SARS-CoV-2 which showed a frequency of (AA, AG, and GG) alleles. Additionally, there was no noticeable linkage between the (GG, CC, and CG) genotypes of IL-6 (−174 G/C) (rs1800795) and the hazard of contracting COVID-19. In conclusion, this investigation confirmed that the TC genotype of ACE2 (rs2106809) polymorphism represents a risk factor for acquiring COVID-19 and proposed to perform a critical action in the severity of pathogenicity in Iraqi Kurdish people.

Comparative characterization of interleukin genotypes and risks of bronchial asthma phenotypes in children

The present paper analyses genetic predictors of various endotypes and phenotypes of bronchial asthma in children. The review of data on the structure and prevalence of single-nucleotide polymorphisms of interleukin genes demonstrates their correlation with the risk of virus-induced and allergen-induced phenotypes of bronchial asthma. Significant differences in genotypes correlate with aberrant production of interleukin and the risks for developing various phenotypes of the disease. The studies into genetic factors indicate the significance of functional polymorphisms of interleukin genes as predictors associated with phenotypes and risk of the disease.

Associations of IL6R and IL10 Gene Polymorphisms with Susceptibility to Ankylosing Spondylitis with or without Acute Anterior Uveitis

ABSTRACT Background This research aims to explore the associations between ten candidate single nucleotide polymorphisms (SNPs) on Interleukin-6 receptor (IL6R) and Interleukin-10 (IL10) genes and ankylosing spondylitis (AS) patients with or without acute anterior uveitis (AAU). Methods This study involved a case-control approach that examined 354 cases with AS and AAU, 377 AS cases without AAU, and 918 healthy controls. Genotyping of ten SNPs of IL10 and IL6R genes was performed using iPLEX Gold genotyping method. The allele and genotype frequencies of cases and healthy individuals were contrasted using the chi-square test. The IL10 mRNA level in various IL10 genotypes was tested using real-time PCR. Results Two loci associated with AS with AAU were identified: IL10//rs3790622 (OR = 0.664; 95%CI = 0.503–0.878; Pc = 0.038); IL10//rs3021094 (OR = 1.365; 95%CI = 1.110–1.679; Pc = 0.032). The other eight loci located on IL10 and IL6R did not show significant associations with the diseases. Additionally, as shown by functional experiments, there was no correlation between the mRNA expression of IL10 and various genotypes. Conclusion Our study suggests that the IL10 gene contributes to the susceptibility of the Chinese population to AS with AAU.

Indirect influence of microRNA-146a on the association of IL-6 and TNF-α genetic polymorphisms with the increased risk of hip osteoarthritis.

Primary osteoarthritis (POA) is a complex hereditary disease that involves the interplay between genetics and epigenetics. MicroRNA molecules play important roles in epigenetic mechanisms. MicroRNA-146a (miR-146a) is a negative regulator of the immune response in osteoarthritis (OA). So, variations in the miR-146a gene could affect OA risk. The aim of this study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the miR-146a, interleukin-6 (IL-6), Toll-like receptor 10 (TLR10), and tumor necrosis factor-alpha (TNFA) genes and the risk for development of advanced-stage primary hip osteoarthritis (PHOA) and primary knee osteoarthritis (PKOA) in the Croatian population. A total of 609 POA patients and 656 healthy donors were genotyped for SNPs in the miR-146a (rs2910164, G>C). Since we used same patients and controls as two studies before us, we already had information about IL-6 (rs1800795, C>G), TLR10 (rs11096957, C>T), and TNFA (rs1800629, C>T) genotypes of our subjects. None of the differences were statistically significant comparing either allelic or genotypic frequencies of miR-146a SNP rs2910164 (G>C) between the PHOA and PKOA patients and controls. However, we found a significant association with risk to PHOA for the combination of genotypes (stratified miR-146a genotype with the IL-6, and stratified miR-146a genotype with the TNFA). In a multifactorial disease such as POA, we have shown the indirect relevance of a second modifying factor (miR-146a), which apparently contributes to the overall risk of PHOA. There was no risk association with the PKOA, indicating that these two localities (hip and knee) might have different risk-modifying factors.

Assessment of association between interleukin 6 gene variant and its serum level in chronic obstructive pulmonary disease in a sample of Egyptian population

Abstract Background Researches in chronic obstructive pulmonary disease (COPD) had shown signs of inflammation with inflammatory markers that had pivotal role in COPD. some studies proposed that elevated serum interleukin-6 (IL-6) is associated with negative impact on lung functions but up to our knowledge, no studies were performed to correlate the genotypes of IL-6 with COPD patients in Egyptian and middle east populations. Objectives To study both the correlation of serum level of IL-6 as well as its gene variant (also known as G174C)) as possible genetic marker for COPD patients in Egyptian patients. Materials and methods This study is case-control that enrolled ninety participants; it consisted of two groups. Group I included 45 patients who were diagnosed as stable COPD; Group II included 45 healthy participants. After full clinical and pulmonary functions assessment of all participants, blood samples were collected from both groups for the detection serum level of IL-6 by ELISA and the detection of IL6 variant by TaqMan Real-Time PCR. Results Our study revealed that there was statistically significant increase in serum level of interleukin-6 in COPD patients compared to normal individuals (P value &lt;0.001) and the presence of G/G variant of interleukin 6 gene in COPD patients more than normal subjects with frequency of 84.4% and 53.3% for COPD patients and healthy controls respectively. There was significant correlation between the serum level of interleukin-6 and COPD staging (P value &lt;0.007). Conclusion The genotype GG variant of IL6 contributes to the prediction of COPD and may be used as a marker for the prediction of COPD risk in Egyptian population. Serum level of IL6 is markedly higher in COPD patients and can be used as a parameter of correlation with COPD stages.

Association of Interleukin-10 Gene Polymorphism with Susceptibility and Severity of Axial Spondyloarthritis

Background: This study aimed to determine the association of Interleukin-10 (IL-10) gene polymorphisms with the susceptibility and severity of axial spondyloarthritis (axSpA) that may guide to have an idea about the genetic basis of the disease and it’s association with severity. Objective: Aim of the study was to demonstrate the IL-10 gene polymorphisms to determine their association with susceptibility and severity of axSpA. Methods: According to Assessment of Spondyloarthritis International Society (ASAS) classification criteria total 38 patients with axSpA (clinically diagnosed by an expert Rheumatologist, attending in outpatient department (OPD) of Rheumatology, Bangabandhu Sheikh Mujib Medical University, BSMMU) and 38 healthy controls (resident doctors, laboratory staffs of BSMMU and general people) after fulfilling the inclusion criteria were enrolled in this study. Blood samples were collected after taking informed written consent and data were collected in a predesigned data collection sheet. The IL-10 gene polymorphisms IL-10 (819T/C), IL-10 (1082A/G) and IL-10 (592C/A) were detected by Polymerase chain reaction- Restriction fragment length polymorphism (PCR- RFLP) method at Department of Microbiology and Immunology, BSMMU, Dhaka. Results: According to BASDAI score, 14 patients were in inactive disease group and 24 patients were in active disease group. The homozygous CC genotype and C allele of IL-10 (-819T/C) were found significantly higher in patients than control group (p=0.022 and p=0.045 respectively). The heterozygous GA genotype of IL-10 (-1082A/G) gene has significant association (p=0.001) with axSpA. It indicates that the homozygous CC genotype and C allele of IL-10 (819T/C) and heterozygous GA genotype of IL-10 (1082A/G) have an association with the susceptibility of axSpA. Conclusion: CC genotype and C allele of IL-10 (-819T/C) and GA genotype of IL-10 (1082A/G) are associated with axSpA susceptibility. But no association of these genotypes were found with disease severity. Bangladesh Med Res Counc Bull 2023; 49: 171-176

Interleukin 10 (IL10) promoter region polymorphism is associated with IL10 serum concentrations and processing speed in healthy community-dwelling older adults

Inflammation is repressed by interleukin 10 (IL10), a potent anti-inflammatory cytokine, and unchecked inflammation can have detrimental effects on cognition. In healthy older adults enrolled in the Australian Research Council Longevity Intervention (ARCLI) cohort we explored whether a known functional single nucleotide polymorphism (SNP) in the promoter region of IL10, −1082 G/A (rs1800896), was associated with reaction times on computerized cognitive testing that included elements of processing speed (i.e., reaction time). Participants were aged 60–75 years (240 females, 158 males), free of dementia and psychiatric disorders, and provide a blood sample. Processing speed was measured using the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB), which includes measures of reaction time (in milliseconds, ms) on six tasks. Blood-derived DNA was genotyped for the IL10 rs1800896 SNP and presence of the APOE E4 allele. General linear models for each SUCCAB subtest were fitted, with age, sex, education (years), APOE E4 carrier status, and IL10 genotype as independent variables. Carriers of the IL10 AA genotype had significantly slower reaction times on multiple tests compared to carriers of the minor allele (AG, GG) and lower IL10 serum levels. Although IL10 SNPs have not been detected in Alzheimer’s disease genome-wide associated studies, these results support further exploration of IL10 mechanisms as a possible resilience factor.

Association between IL-6 polymorphisms and Atopic Dermatitis in Chinese Han children.

Atopic Dermatitis (AD) is a chronic inflammatory skin disease that affects almost 20% of children and 2 -10% of adults worldwide. Previous studies revealed that Interleukin-6 (IL-6) plays an essential role in autoimmune and chronic inflammatory diseases. This study aims to investigate the associations between IL-6 polymorphisms and AD. Blood samples were collected from 132 AD patients and 100 controls, and single nucleotide polymorphisms (SNPs) in IL-6 (rs2069840 (C/G), rs2066992 (G/T), rs2069837 (A/G) and rs1800796 (G/C)) were analyzed using Multiplex PCR-Based Next Generation Sequencing (NGS). Results showed that the A/G genotype of IL-6/rs2069837 was significantly associated with a 1.933-fold increased risk of AD compared to those patients with A/A genotype (OR 1.933; 95%CI 1.086-3.438; p=0.024). The combined A/G-G/G genotype raised AD risk by 1.856 times compared to patients with the A/A genotype in dominant model (OR: 1.856; 95% CI: 1.056-3.261; p=0.030). No association was observed for 3 other SNPs and 4 haplotypes. These findings suggested that the A/G genotype of IL-6/rs2069837 was more susceptible to AD than A/A genotype in Chinese Han children, indicating the risk role of IL-6/rs2069837 in the occurrence of AD.

Effects of Interleukin-1 Genotype on the Clinical Efficacy of Non-Surgical Periodontal Treatment of Polish Patients with Periodontitis

(1) Background: Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth-supporting apparatus. The aim of the study was to evaluate the efficacy of basic periodontal treatment depending on the interleukin-1 genotype in adult Poles. (2) Methods: Sixty subjects aged 39-64 years were examined. At initial presentation (T1), at 6-8 weeks (T2), and 16-18 weeks (T3) after treatment completion, the following percentages were recorded: surfaces with plaque, pockets bleeding, pocket depth, and change in the attachment level. During the T1 examination, the genotype for IL-1 was determined using the GenoType® PST test. (3) Results: Thirty subjects had genotype IL+ and the other thirty were IL-. During the T1 examination no significant differences were observed between patients. The study showed an increase of all the tested clinical parameters after 6-8 weeks. This increase continued up to the T3 examination. A significant reduction in the percentage of plaque surfaces after 6-8 weeks was observed, which was sustained after 16-18 weeks for both genotypes. For both genotypes, a significant decrease in the percentage of bleeding pockets was observed at the T2 examination, which persisted through until examination T3. For both studied genotypes, after 6-8 weeks, a significant shallowing of pockets was observed. In patients with the IL- genotype, a further significant shallowing of pockets was observed after 16-18 weeks. A significant reconstruction of epithelial attachment was observed between the T1 and T2 examinations, averaging 0.55 mm in patients with the IL+ genotype, and 0.77 in patients with the IL- genotype. (4) Conclusions: The results of our study show that the IL-1 genotype, may be one of the factors affecting the healing process after non-surgical periodontal treatment in adult Poles.

Evaluation of interleukin 10, interleukin 1-beta, and tumor necrosis factor-alpha gene polymorphisms in patients with periodontitis and healthy controls

BackgroundChronic periodontitis (CP) is a prevalent infectious disease caused by an interplay between pathogens and immune responses. Gene polymorphisms are among the factors that affect susceptibility to CP. This study aimed to assess the association between CP and single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) genes.MethodsA total of 87 patients with CP and 89 healthy controls were included in this study. Venous blood samples were obtained, and DNA was extracted and purified. Segments containing the relevant genes were amplified by polymerase chain reaction (PCR). Electrophoresis was performed after restriction fragment length polymorphism (RFLP) to determine genotype and allele frequencies.ResultsThe CP group showed significantly different allele and genotype frequencies for three out of five SNPs: IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, and IL-1ß + 3954 C/T (p < 0.05). Additionally, the frequency of the TNF-α ─ 857 AA genotype was significantly lower in patients compared with controls (p = 0.034); however, no significant differences were found in allele frequencies (p > 0.05). Logistic regression analysis revealed that carriers of IL-10 ─ 592 A allele and IL-1ß + 3954 T allele are at higher risk of CP (p < 0.001). Allele and genotype frequencies for TNF-α ─ 308 G/A did not differ significantly between patients and controls (p > 0.05).ConclusionsThis study showed specific genotypes of IL-10 ─ 592 C/A, IL-10 ─ 819 C/T, IL-1ß + 3954 C/T, and TNF-α ─ 857 G/A SNPs may be associated with an increased risk of CP development.

Race, Interleukin-6, TMPRSS6 Genotype, and Cardiovascular Disease in Patients With Chronic Kidney Disease.

Background Differences in death rate and cardiovascular disease (CVD) between Black and White patients with chronic kidney disease is attributed to sociocultural factors, comorbidities, genetics, and inflammation. Methods and Results We examined the interaction of race, plasma IL-6 (interleukin-6), and TMPRSS6 genotype as determinants of CVD and mortality in 3031 Chronic Renal Insufficiency Cohort study participants. The primary outcomes were all-cause mortality and a composite of incident myocardial infarction, peripheral artery disease, stroke, and heart failure. During the median follow-up of 10 years, Black patients with chronic kidney disease experienced a significantly higher mortality (34% versus 26%) and CVD composite (41% versus 28%) compared with White patients. After adjustment, TMPRSS6 genotype did not associate with the outcomes. The adjusted hazard ratio for mortality (4.11 [2.48-6.80], P<0.001) and CVD composite (2.52 [1.96-3.24], P<0.001) were higher for the highest versus lowest IL-6 quintile. The adjusted hazards for death per 1-quintile increase in IL-6 in White and Black individuals were 1.53 (1.42-1.64) versus 1.29 (1.20-1.38) (P<0.001), respectively. For CVD composite they were 1.61 (1.50-1.74) versus 1.30 (1.22-1.39) (P<0.001), respectively. In Cox proportional hazard models that included IL-6, there was no longer a racial disparity for death (1.01 [0.87-1.16], P=0.92), but significant unexplained mediation remained for CVD (1.24 [1.07-1.43]; P=0.004). Path models that included IL-6, diabetes, and urine albumin to creatinine ratio were able to identify variables responsible for racial disparity in mortality and CVD. Conclusions Racial differences in mortality and CVD among patients with chronic kidney disease could be explained by good-fitting path models that include selected mediator variables including diabetes and plasma IL-6.

Effects of Infection-Induced Fever and the Interaction with IL6 rs1800796 Polymorphism on the Prognosis of Breast Cancer.

Previous studies have found that acute febrile infection may decrease the risk of breast cancer. Meanwhile, it is well known that interleukin-6 (IL6) played dual roles in the tumor microenvironment. Fever may stimulate IL6 production, and IL6 rs1800796 also influences the expression of IL6. However, the impact of fever and its interaction with IL6 rs1800796 on breast cancer survival remains to be explored. This was a prospective cohort study of 4,223 breast cancer patients. Exposures were pre-/postdiagnostic infection-induced fever and rs1800796 polymorphism. The endpoints were overall survival (OS) and progression-free survival (PFS). Adjusted hazard ratios were obtained using multivariate Cox proportional hazards regression models. Compared with women without prediagnostic fever, the adjusted hazard ratio (HR) of progression for those with prediagnostic fever was 0.81 (95% CI, 0.66-0.99), particularly for the CC genotype of IL6 rs1800796 (HR, 0.53; 95% CI, 0.36-0.79). OS was also better (HR, 0.59; 95% CI, 0.36-0.99) among women with the CC genotype exposed to prediagnostic fever, accompanied by a significant interaction (P = 0.021). Postdiagnostic fever conferred better PFS for breast cancer (HR, 0.72; 95% CI, 0.52-1.00). Irrespective of the genotype of IL6, lymph node-positive women with postdiagnostic fever (HR, 0.57; 95% CI, 0.37-0.89) had a lower risk of progression than lymph node-negative women (HR, 1.12; 95% CI, 0.70-1.79). Infection-induced fever was beneficial to breast cancer survival, particularly for women who were the CC genotype of IL6 rs1800796 or node positive. This study provides new insight into the roles of infection-induced fever as a potential prognostic marker and therapy regimen for breast cancer.

Association of IL-6 genotypes with their serum levels among Iraqi patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a complex autoimmune system disease and significant impact on the health of the population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. Interleukin-6 (IL-6) is a common pro-inflammatory cytokine that has several roles in a variety of pathophysiologic systems, most notably in the development of rheumatoid arthritis (RA). This study aims to investigate the association of polymorphism of the “IL-6 174 G/C rs(1800795) gene” to their serum levels among Iraqi patients. A total of 60 participants (40 confirmed rheumatoid arthritis patients and 20 controls) were selected using a convenient sampling method. “Genetic polymorphism of IL-6 174 G/C rs(1800795)” was carried out using RFLP-PCR. Serum levels of IL-6 were performed using by enzyme-linked immunosorbent assay technique (ELISA) using a Human- IL-6 kit. Based on the polymorphism of IL-6 174 G/C rs(1800795), serum levels of IL-6 were higher among rheumatoid arthritis patients with CC and GC genotypes than that with GG genotypes (CC, 137.5336±35, GC 135.0622±70.88476and GG 65.5587±1.77873, P &lt; 0.05. Furthermore, patients with GG genotype had the lowest IL-6 level with an insignificant difference compared to controls1. 65.5587±1.77873vs. 59.8203±1.30673,P&gt; 0.05.

Interleukin-1 receptor antagonist (IL-1RA) and interleukin-4 (IL-4) variable number of tandem repeat polymorphisms in schizophrenia and bipolar disorder: an association study in Turkish population

BackgroundPro-inflammatory/anti-inflammatory cytokine imbalance in cerebrospinal fluid or plasma of schizophrenia (SCZ) and bipolar disorder (BD) patients has been documented over the last decade. We aim to examine the interleukin-1 receptor antagonist (IL-1RA) and IL-4 variable number of tandem repeat (VNTR) polymorphisms in SCZ and BD patients by comparing them with healthy controls.MethodsTwo hundred and thirty-four unrelated patients (127 patients with SCZ, 107 patients with BD) and 204 healthy controls were included. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis. In addition, the polymerase chain reaction technique was used to investigate IL-1RA and IL-4 VNTR polymorphisms.ResultsOur results showed that the distributions of IL-1RA and IL-4 genotype and the allele frequencies of SCZ or BD patients were not significantly different from the healthy control group. IL-1RA allele 2 homozygous genotype and IL-1RA allele 2 frequencies were non-significantly higher among SCZ patients than in controls.ConclusionsOur study indicates that the IL-1RA and IL-4 VNTR polymorphisms are not considered risk factors for developing SCZ and BD among Turkish patients.

Role of Interleukin-10 (1082G/A) and Splicing Factor 3B Subunit 1 (2098A/G) Gene Polymorphisms in Chronic Lymphocytic Leukemia

OBJECTIVE: Interleukin-10 (IL-10) gene polymorphisms might play a part in the development of some malignant tumors. It has been linked with high bcl-2 expression in some B-lymphocyte malignancies. Its relationship with chronic lymphocytic leukemia (CLL) development is still under investigation. Other studies have linked Splicing Factor 3B Subunit 1 (SF3B1) mutations to a poorer prognosis of CLL. From this context, we have great interest to investigate the effect of both IL-10 (1082G/A) and SF3B1 (2098A/G) gene polymorphisms on CLL in this study. MATERIALS AND METHODS: Peripheral blood mononuclear cells were analyzed for IL-10 (1082G/A) and SF3B1 (2098A/G) gene polymorphisms by real-time quantitative polymerase chain reaction in 80 newly diagnosed CLL patients and 80 controls. RESULTS: Our results showed that the IL-10 (G/A) genotype, IL-10 (A/A) genotype and IL-10 A allele and SF3B1 (A/G) genotype and SF3B1 G allele were increased significantly in the patients group compared with the control group. CONCLUSION: IL-10 gene polymorphisms (1082 G/A and A/A) and A alleles might be associated with increased risk of CLL development compared with G/G genotypes and G alleles and are a probable risk factor for the disease. Also, our study demonstrated that SF3B1 (2098A/G) polymorphisms and G allele are related to and might be a causative factor for CLL.