Nucleotide Polymorphisms In Interleukin Research Articles

Association of three single nucleotide polymorphisms in interleukin 6 gene with risk of chronic obstructive pulmonary disease

BackgroundsExperimental studies have implicated the involvement of interleukin 6 (IL6) in chronic obstructive pulmonary disease (COPD), supporting the possible association between genetic alterations in IL6 gene and risk of COPD. ObjectivesWe aimed to examine the association of three polymorphisms in IL6 gene with COPD by integrating the summary results of available reports, and summarize the changes circulating IL6 concentrations across genotypes. MethodsTwo investigators independently searched medical literature, selected qualified publications, assessed study quality, and abstracted detailed information. STATA software v14.1 was applied for statistical analyses. ResultsTen articles, including 18 independent studies and 4 815 participants, were comprehensively pooled. When all studies were analyzed together, the association with COPD was not significant for rs1800795 and rs1800797, yet statistical significance was attained for rs1818879 (P < 0.05) across four genetic modes of inheritance. When analyses were restricted to preset subgroups, race, matched condition, and COPD diagnosis were identified as the factors attributed to heterogeneity between studies. Moreover, changes in circulating IL6 concentrations remained nonsignificant across the genotypes of rs1800795 and rs1818879 (P > 0.05). Funnel plots and related tests revealed a low likelihood of publication bias for three studied polymorphisms (P > 0.1). ConclusionsOur findings indicated that IL6 gene rs1818879 might be a COPD-susceptibility locus. Further validations in longitudinal studies are necessary.

Retraction: Novel Single Nucleotide Polymorphisms in Interleukin 6 Affect Tacrolimus Metabolism in Liver Transplant Patients.

Retraction: Novel Single Nucleotide Polymorphisms in Interleukin 6 Affect Tacrolimus Metabolism in Liver Transplant Patients.

The prognostic value of IL10 and TNF alpha functional polymorphisms in premenopausal early-stage breast cancer patients.

BackgroundInterleukin-10 and tumor necrosis factor α play an important role in breast carcinogenesis. Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription. This study analyzes single nucleotide polymorphisms in interleukin 10 and tumor necrosis factor α genes and their contribution to breast cancer phenotype, lymph node status and survival in a group of young Lithuanian women with early-stage breast cancer patients.ResultsWe genotyped 100 premenopausal Eastern European (Lithuanian) patients with stage I-II breast cancer, ≤50 years old at the time of diagnosis, for interleukin 10 -592A > C, −819C > T and -1082A > G and tumor necrosis factor α -308G > A single nucleotide polymorphisms in the gene promoter region. We used the polymerase chain reaction, namely a restriction fragment length polymorphism method, for a SNP analysis. All genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the HapMap CEU population. Holders of IL10 -592A > C heterozygous IL10 -592 AC genotype had a higher probability of estrogen receptor positive breast cancer phenotype than homozygous variants (P = 0.017). Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017). Of all the tested single nucleotide polymorphisms, only TNFα -308G > A has revealed a prognostic capability for breast cancer survival. GA genotype carriers, compared to GG, showed a significant disadvantage in progression-free survival (P = 0.005, adjusted hazard ratio (HR) = 4.631, 95 % confidence interval (CI) = 1.587 – 13.512), metastasis-free survival (P = 0.010, HR = 4.708, 95 % CI = 1.445 – 15.345) and overall survival (P = 0.037, HR = 4.829, 95 % CI = 1.098 – 21.243).ConclusionsAccording to our data, IL10 -1082A > G, −819 T > C, −592A > C polymorphisms and phased haplotypes have not revealed a prognostic value for breast cancer. On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.

Novel Single Nucleotide Polymorphisms in Interleukin 6 Affect Tacrolimus Metabolism in Liver Transplant Patients

BackgroundTacrolimus is the first-line immunosuppressant after organ transplantation. It is mainly metabolized by cytochrome P450, family 3, subfamily A (CYP3A) enzymes, but there are large individual differences in metabolism. Interleukin 6 (IL6) has been shown to cause a pan-suppression of mRNA levels of ten major CYP enzymes in human hepatocyte cultures. IL6 has been shown to provide hepatoprotection in various models of liver injury. Rs1800796 is a locus in the IL6 gene promoter region which regulates cytokine production. We speculated that IL6 rs1800796 polymorphisms may lead to individual differences in tacrolimus metabolism by affecting CYP3A enzymes levels and liver function after liver transplantation.Methodology/Principal FindingsNinety-six liver transplant patients receiving tacrolimus were enrolled in the study. Two single nucleotide polymorphisms (SNP), CYP3A5 rs776746 and IL6 rs1800796, were genotyped in both donors and recipients. The effects of SNPs on tacrolimus concentration/dose (C/D ratio) at four weeks after transplantation were studied, as well as the effects of donor IL6 rs1800796 polymorphisms on liver function. Both donor and recipient CYP3A5 rs776746 allele A showed association with lower C/D ratios, while donor IL6 rs1800796 allele G showed an association with higher C/D ratios. Donor CYP3A5 rs776746 allele A, IL6 rs1800796 allele C, and recipient CYP3A5 rs776746 allele A were associated with fast tacrolimus metabolism. With increasing numbers of these alleles, patients were found to have increasingly lower tacrolimus C/D ratios at time points after transplantation. Donor IL6 rs1800796 allele G carriers showed an association with higher glutamic-pyruvic transaminase (GPT) levels.ConclusionsCombined analysis of donor CYP3A5 rs776746, IL6 rs1800796, and recipient CYP3A5 rs776746 polymorphisms may distinguish tacrolimus metabolism better than CYP3A5 rs776746 alone. IL6 may lead to individual differences in tacrolimus metabolism mainly by affecting liver function.

Association of single nucleotide polymorphisms in interleukin 12 ( IL-12A and -B) with asthma in a Chinese population

Increasing evidence has indicated that genetic variants may contribute to immune dysregulation and susceptibility to noninfectious inflammatory diseases. Cytokines, including interleukin 12 (IL-12), play a key role in the regulation of the immune system. The aim of this study was to investigate whether single nucleotide polymorphisms (SNP) in IL- 12A and IL-12B were associated with asthma in a Chinese population. Genotype characteristics were determined in 197 asthma patients and 369 controls by the polymerase chain reaction–restriction fragment length polymorphism method and DNA sequencing assay. The genotype and allele frequencies of IL-12A rs568408 demonstrated significant differences between cases and controls ( p < 0.001). The AC genotype of rs3212227 was associated with a significantly decreased risk of asthma compared with the AA genotype ( p = 0.036). The subjects carrying combined genotypes (rs568408 AG and rs3212227 AC/CC) at both loci had a 2.05-fold increased asthma risk compared with those carrying all other genotypes ( p = 0.001). In contrast, individuals carrying combined genotypes of rs568408 GG and rs3212227 AC/CC were associated with a significantly decreased risk of asthma compared with those carrying the combined genotypes of rs568408GG and rs3212227AA ( p = 0.009). No significant difference was reported for rs2243115 between cases and controls. These results suggest that the SNPs in IL-12A rs568404 and IL-12B rs3212227 may individually and jointly contribute to the risk of asthma in a Chinese population.

Association of Helicobacter pylori Infection With Reduced Risk for Esophageal Cancer Is Independent of Environmental and Genetic Modifiers

Infection with Helicobacter pylori is associated with reduced risk of esophageal adenocarcinoma (EAC), but it is not clear whether this reduction is modified by genotype, other host characteristics, or environmental factors. Furthermore, little is known about the association between H pylori and adenocarcinomas of the esophagogastric junction (EGJAC) or squamous cell carcinomas (ESCC). We sought to measure the association between H pylori infection and esophageal cancer and identify potential modifiers. In an Australian, population-based, case-control study, we compared the prevalence of H pylori seropositivity and single nucleotide polymorphisms in interleukin (IL)-1B (-31, -511) and tumor necrosis factor (TNF)-alpha (-308, -238) among 260 EAC, 298 EGJAC, and 208 ESCC patients and 1346 controls. To estimate relative risks, we calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression in the entire sample and within strata of phenotypic and genotypic risk factors. H pylori infection was associated with significantly reduced risks of EAC (OR, 0.45; 95% CI: 0.30-0.67) and EGJAC (OR, 0.41; 95% CI: 0.27-0.60) but not ESCC (OR, 1.04; 95% CI: 0.71-1.50). For each cancer subtype, risks were of similar magnitude across strata of reflux frequency and smoking status. We found no evidence that polymorphisms in IL-1B or TNF-alpha modified the association between H pylori and EAC or EGJAC. H pylori infection is inversely associated with risks of EAC and EGJAC (but not ESCC); the reduction in risk is similar across subgroups of potential modifiers.

Cytokine gene polymorphisms and cancer-related symptoms in lung cancer patients

9012 Background: Cytokines, aberrantly produced by cancer cells, have recently been implicated in the severity of cancer-related symptoms. We hypothesize that functional variations in cytokine genes could explain variability in self-reported pain and depressed mood in lung cancer patients of all stages. Methods: Pain, depressed mood, clinical and demographic variables were assessed at presentation, and prior to initiating any cancer treatment in 514 white patients with non-small cell lung cancer (NSCLC). Using the TaqMan method, we genotyped single nucleotide polymorphisms in interleukin (IL) −6 (−174 G&gt;C), IL-8 (−251 T&gt; A), and tumor necrosis factor-alpha (TNF-; −308 G&gt; A), and determined their associations with pain and depressed mood. Results: Sixteen and 7% of respondents reported severe levels of pain (≥ 7, on a 0–10 scale) and depressed mood most/all of the time, respectively. The severity of pain and depressed mood predictably varied by clinical, sociodemographic, and genotype variables in the univariate analyses. Multivariable logistic regression analyses showed that variant allele in IL8 (OR=2.05;95%CI=1.04–4.06), early age of onset (≤ 50 years) (OR=1.80;95%CI=1.02–3.14), and depressed mood (OR=4.55;95%CI=2.105–9.81) were significant predictors for severe pain. For depressed mood, results showed that variant allele in IL6 (OR=0.49;95%CI=0.24–0.49), severe pain (OR= 3.77;95%CI=1.79–7.95) and a history of stroke (OR=3.50;95%CI=1.03–11.82) as significant predictors. Classification and Regression Tree analyses revealed potential higher order gene-gene interaction for pain (IL1 and IL6) and depressed mood (IL8 and IL6). Conclusions: Variations in individual inflammatory responses could partly explain variability in pain and depressed mood in patients with lung cancer. No significant financial relationships to disclose.

Polymorphisms in Inflammation Genes and Bladder Cancer: From Initiation to Recurrence, Progression, and Survival

Since chronic inflammation contributes to tumorigenesis, we hypothesized that the risk and clinical outcome of bladder cancer (BC) might be modulated by genetic variations in inflammation genes. Using the TaqMan method, we genotyped single nucleotide polymorphisms in interleukin (IL) -6 (-174 G-->C), IL-8 (-251 T-->A), tumor necrosis factor-alpha (TNF-alpha; -308 G-->A), and peroxisome proliferator-activated receptor gamma (PPARG; Pro12Ala), and determined their associations with BC initiation and clinical outcome. We found that the IL-6 variant genotype (C/C) was associated with an increased BC risk (OR, 1.77; 95% CI, 1.25 to 2.51). There were joint effects between the variant IL-6 genotypes and smoking status, and between the variant genotypes of IL-6 and other genes. To assess effect on recurrence, we grouped non-muscle-invasive BC patients according to intravesical Bacillus Calmette-Guerin (BCG) treatment status: no BCG, induction BCG (iBCG), and maintenance BCG (mBCG). In the Cox proportional hazards model, the variant IL-6 genotype was associated with an increased recurrence risk (hazard ratio [HR], 4.60; 95% CI, 1.24 to 17.09) in patients receiving mBCG. The variant PPARG genotype was associated with a reduced recurrence risk (HR, 0.41; 95% CI, 0.20 to 0.86) among untreated patients. In patients with non-muscle-invasive BC, the variant IL-6 genotype was associated with an increased progression risk (HR, 1.88; 95% CI, 0.80 to 4.11). In patients with invasive BC, variant IL-6 was associated with improved 5-year overall and disease-specific survival (HR, 0.43; 95% CI, 0.19 to 0.94 and HR, 0.39; 95% CI, 0.15 to 1.00, respectively). Inflammation gene polymorphisms are associated with modified BC risk, treatment response, and survival.