IL-10 Haplotypes Research Articles

IL-10 polymorphism genotypes, haplotypes, and diplotypes are associated with colorectal cancer predisposition and outcome in Tunisian population

Background and aimAs the presence of single nucleotide polymorphisms (SNPs) in the interleukin (IL)-10 gene continues to be a major challenge in the development of effective therapies for digestive cancers, this case-control study was conducted to assess the possible influence of genotype, haplotype and diplotype for two SNPs (−1082A/G (rs1800896) and −592A/C (rs1800872)) located in the promoter region of IL-10 gene on the incidence, severity and prognosis of colorectal cancer (CRC) in Tunisians. MethodsIL-10 gene SNPs were analyzed in 130 CRC cases and 165 healthy subjects (HS) using PCR-SSP. ResultsFor the IL-10 -1082A/G SNP, the comparison of genotype frequencies between cases and HS groups showed that the G allele significantly reduced CRC risk under the recessive model (GG vs. AA + AG: OR [95%CI] = 0.44 [0.21–0.93], p = 0.03). Conversely, a positive association was observed between the codominant model (AG vs. AA + GG) and high susceptibility (OR [95%CI] = 1.65 [1.02–2.63], p = 0.04). After stratification by disease site, the recessive model was also found to reduce susceptibility to colon cancer (OR [95%CI] = 0.18 [0.04–0.72], p = 0 0.01), while the homozygote model (AA vs. GG) was suggested as a risk factor (OR [95%CI] = 5.16 [1.31–23.26], p = 0.02). Furthermore, the codominant model (AG vs. AA + GG) doubled the risk of rectum cancer (OR [95%CI] = 1.98 [1.07–3.70], p = 0.03). For the IL-10 -592A/C SNP, the codominant model (AC vs. AA + CC) has a protective effect against the development of CRC (OR [95%CI] = 0.59 [0.36–0.94], p = 0.03). The IL-10 gene haplotype was not associated with CRC risk. A stratified analysis by disease site demonstrated that the presence of Hap3 (−1082G and −592C alleles) specifically reduced the risk of developing colon cancer (OR [95%CI] = 0.51 [0.32–0.80], p = 0.003). Moreover, homozygous Hap3/Hap3 diplotype significantly reduced susceptibility to CRC (OR [95%CI] = 0.35 [0.14–0.85], p = 0.02). Interestingly, this diplotype has not been identified in colon cancer patients. Kaplan-Meier analysis showed that the homozygous Hap2/Hap2 diplotype was significantly associated with decreased overall survival (Log-rank: p = 0.01). This association was also observed in the colon cancer subgroup (Log-rank: p = 0.001). ConclusionOur findings provide preliminary indications that the −1082A/G and −592/AC SNPs within the IL-10 gene may exhibit significant associations with the pathogenesis and prognostic outcomes of CRC. However, further investigations are still warranted to validate and establish the veracity of our findings.

No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients.

A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.

Analysis of Mutational Status of IGHV, and Cytokine Polymorphisms as Prognostic Factors in Chronic Lymphocytic Leukemia: The Romanian Experience.

The aim of the current study was to assess the associations between genetic risk factors (such as the mutational status of the IGHV gene and polymorphisms of the IL-10 and TNF-α genes) and CLL risk, prognosis, and overall survival. Another goal of this study was to evaluate the multivariate effect of the combination of multiple genetic risk factors (mutational status of the IGHV gene, somatic mutations, DNA CNVs, and cytokine SNPs) on the clinical characteristics and survival of patients. A total of 125 CLL patients and 239 healthy controls were included for comparative SNP analysis. IL-10 (rs1800896 and rs1800872) and TNF-α (rs361525 and rs1800750) SNPs and haplotypes were not associated with CLL risk. The absence of hypermutation in the IGHV gene was shown to be of important prognostic value, being associated with short OS. Further individual risk factors for short OS were an age above 65 years at diagnosis and the presence of somatic mutations and/or CNVs. In our multivariable analysis, the presence of somatic mutations and the IL-10 rs1800872 variant allele, and the association of CNVs with the IL-10 rs1800896 variant allele, were identified as risk factors for short OS. Moreover, the OS in unmutated IGHV patients was additionally affected (decreased) by the presence of CNVs and/or somatic mutations. Similarly, IL-10 rs1800896 modulated the OS in unmutated IGHV patients with CNVs.

Investigation of the Relationship between IL-6, IL-6R and CXCL5 Polymorphisms and Obesity in Denizli Province of Turkey

Obesity and its effects on increasing morbidity and mortality have reached the level of an epidemic with a high frequency in modern populations. IL-6 released from adipose tissue is known to trigger the chronic inflammation in obesity. CXCL5, which mediates the activation and migration of neutrophils, has been found at high levels in obese subjects. In our study, we aimed to investigate the possible effects of IL-6, IL-6R and CXCL5, polymorphisms and haplotypes on the development of obesity. We studied IL-6, rs2069827 (-1363, G/T), rs1800797 (-597, G/A), rs1800796 (-572, G/C) and rs1800795 (-174, G/C), IL-6R rs4845617 (-183, G/A), rs2228145 (+48892, A/C) and CXCL5 rs352046 (-156, G/C) polymorphic sites in 60 obesity patients and 59 healthy controls. For genotyping we used PCR-RFLP based approach. The IL-6 rs1800796, rs1800795 and IL-6R rs4845617 G allelles could be the possible genetic factors responsible for obesity. We found similar results in female obese group. The results indicated that there was no association between obesity and other SNPs (rs2069827, rs1800797, and rs1800795 and rs2228145) and CXCL5, rs352046. The results of IL-6 and IL-6R haplotype analysis by global differentiation test showed that haplotypes may have different distributions between obese and controls. Our results showed that polymorphisms and possible haplotypes in IL-6 and IL-6R genes, which have an important role in inflammation, may affect the development of obesity. This study points out the necessity of investigating the possible effects of gene polymorphisms of other cytokines and their receptors in the development of obesity in larger populations.

Effect of IL6 -174 G/C Gene Polymorphism on Response to Interleukin-6 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis

Objective: The main objective of this study was to evaluate the association of IL6-174 G/C gene polymorphisms and the response to tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (s-JIA).
 Methods: Sixty patients with s-JIA (37 males and 23 females with median age at onset of 5.2 years) who received TCZ were recruited. Basic demographic, laboratory and clinical data were collected alongside the IL-6 haplotype status. The overall response to treatment with TCZ was assessed according to a number of variables including the extent of disease activity reduction, the achievement of clinically inactive disease, the necessity to switch to another biologic disease modifying anti-rheumatic drug (bDMARD) and the achievement of a glucocorticoid-free state.
 Results: Three IL6 -174 genotypes, including, GG, GC, and CC were found with higher frequencies of GC genotype. These genotypes had non-significant association with the response of s-JIA patients to IL-6 blockade in this cohort study. However, a longer time frame from disease onset to diagnosis was associated with poorer long-term treatment response.
 Conclusion: We observed no significant impact of IL6 -174 G/C gene polymorphisms on treatment response to TCZ in s-JIA Egyptian patients. The observation that a shorted timeframe between symptom onset and diagnosis is associated with better long-term response to TCZ provides evidence for a therapeutic “window of opportunity” in patients with s-JIA.

Association between interleukin-10 polymorphisms and juvenile idiopathic arthritis: a meta-analysis.

The aim of this review is to investigate IL-10 polymorphisms (-1082 G/A, -819 C/T, and -592 C/A) and their association with susceptibility to JIA. A meta-analysis was conducted after database search for relevant articles (MEDLINE and EMBASE). A total of seven studies involving 1495 patients and 1670 controls were considered in the meta-analysis. There was no association between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and JIA in allele contrast and any of the genetic models (allele contrast: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.79-1.02, P=0.09; OR=0.97, 95% CI 0.83-1.13, P=0.68; OR=0.92, 95% CI 0.81-1.06, P=0.24, respectively). In subgroup analysis, none of the subtypes of JIA including systemic, rheumatoid factor (RF)-positive polyarticular, RF-negative polyarticular, and oligoarticular was not significantly associated with IL-10 polymorphism. Meta-analysis of the IL-10 haplotype revealed no association between GCC, ACC, and ATA haplotypes and JIA. This meta-analysis showed that IL-10 polymorphisms were not associated with risk of JIA.

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.

Association of IL-10 and TNF-\u03b1 polymorphisms with risk and aggressiveness of hepatocellular carcinoma in patients with HCV-related cirrhosis

BackgroundHepatitis C virus (HCV) infection is a significant risk factor for cirrhosis and hepatocellular carcinoma (HCC) that carry a high mortality. The study aims to investigate the effect of tumour necrosis factor (TNF)-α and interleukin (IL)-10 polymorphisms on risk and pattern of HCC in patients with HCV-related cirrhosis.ResultsThe mean age of the HCC group was 56.21 ± 4.62 years and 54.27 ± 7.63 years for the cirrhotic group. The GG genotype of TNF-ɑ and TT genotype of IL-10 showed a higher incidence of HCC in comparison to the cirrhotic group with P = 0.01 and 0.004. On the calculation of the aggressiveness index (AgI), the TT haplotype was significantly associated with more aggressive tumours in contrast to the other haplotypes with P < 0.001. There is a significant association of portal vein thrombosis, ascites and high AgI with the GG haplotype in contrast to the other haplotypes with P = 0.002, 0.029 and < 0.001, respectively, as regards TNF-α. High AgI (C) was associated with the TT haplotype of IL-10 and GG haplotype of TNF-ɑ.ConclusionOur data bring an essential association of IL-10 and TNF polymorphism with the occurrence of HCC in patients with HCV-related liver cirrhosis. The GG haplotype of TNF-ɑ and TT/AT haplotype of IL-10 are associated with the more aggressive pattern of HCC, so those patients must be treated as early as possible.

Interleukin Gene Variability and Periodontal Bacteria in Patients with Generalized Aggressive Form of Periodontitis.

Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms in IL-1 gene cluster, IL-6 and its receptor, IL-10, IL-17A, and IL-18 were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphism IL-10 −1087 A/G (rs1800896) and specific IL-10 haplotypes were associated with the development of the disease (p < 0.05, Pcorr > 0.05). Four bacterial species occurred more frequently in AgP than in controls (p < 0.01, Pcorr < 0.05). Elevated IL-10 levels were found in AgP patients, carriers of IL-10 −1087GG genotype, and PBMCs stimulated by periodontal bacteria (p < 0.05, Pcorr > 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression of IL-10 and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.

Investigation of genetic susceptibility to Mycobacterium tuberculosis (VDR and IL10 genes) in a population with a high level of substructure in the Brazilian Amazon region

ObjectivesTuberculosis (TB) is an infectious and contagious disease that has been very influential in human history and presents high rates of mortality. The objective of this study was to investigate the association of VDR, IL10, and SLC11A1 gene polymorphisms with susceptibility to the presence of Mycobacterium tuberculosis infection. MethodsA total of 135 patients with confirmed TB and 141 healthy individuals were included in the analysis. Blood samples were collected for DNA extraction. Genotyping of the polymorphisms in the VDR and IL10 genes was performed by real-time PCR, and genotyping of the polymorphisms in the SLC11A1 gene by conventional PCR, followed by visualization in polyacrylamide gel. The genomic ancestry was obtained using an autosomal panel with 48 insertion/deletion ancestry-informative markers. ResultsPolymorphisms TaqI (TT, p=0.004), FokI (CC and CC+CT, p=0.012 and p=0.003, respectively), and BsmI (GG, p=0.008) in the VDR gene, as well as A-592C (GC+AG, p=0.001) in the IL10 gene, were significantly associated with susceptibility to TB In addition, high production of VDR combined with low production of IL10 showed protection for the TB group (p=0.035). ConclusionsThe VDR polymorphisms may confer an increased risk and the IL10 haplotype may be a protection factor for the presence of M. tuberculosis infection in the Brazilian population.

Association of angiogenesis and inflammation-related gene functional polymorphisms with early-stage breast cancer prognosis.

Genetic variations in inflammation- and angiogenesis-related genes may alter the coded protein level and impact the pathogenesis of breast cancer (BC). The present study investigated the association of functional single nucleotide polymorphisms (SNPs) in the VEGFA, IL-1β, IL-1α and IL-6 genes with the early-stage BC phenotype and survival. Genomic DNA and clinical data were collected for 202 adult Eastern European (Lithuanian) women with primary I–II stage BC. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Nine VEGFA, IL-1β, IL-1α and IL-6 polymorphisms were analysed. The VEGFA and IL-6 haplotypes were inferred using Phase software. Patients were prospectively followed-up for recurrence, occurrence of metastasis and mortality until April 30, 2019. All studied genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the 1,000 Genomes project Phase 3 dataset for European population. Significant associations of the studied SNPs with clinicopathologic variables were observed between IL-1α rs1800587 C allele and larger primary tumour size; IL-6 rs1800797 A allele, rs1800797 GA genotype, rs1800795 C allele, IL-6 (rs1800797-re1800795) AC diplotype and hormonal receptor-positive disease; IL-6 rs1800797 A allele and HER2 negative status. In univariate Cox survival analysis, IL-1α rs1800587 CC and IL-6 rs1800797 GG genotype carriers exhibited worse disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS). The IL-6 rs1800795 GG genotype was associated with worse OS. IL-6 (rs1800797, rs1800795) GG/GG diplotype carriers had shorter MFS and OS. Multivariate Cox survival analysis revealed that the IL-1α rs1800587 CC genotype was an independent negative prognostic factor for DFS, MFS and OS, and the IL6 GG/GG diplotype was an independent negative prognostic factor for MFS and OS. According to the present study, functional SNPs in the IL-1α and IL-6 genes may contribute to the identification of patients at higher risk of BC recurrence, development of metastases and worse OS among early-stage patients with BC.

Single nucleotide polymorphism of transforming growth factor-β1 and interleukin-6 as risk factors for ovarian cancer.

IntroductionWe investigated the association between common variants in TGF-β1, IL-6 and the risk of ovarian cancer (OC) in Tunisian patients and control women.Material, methods and resultsStudy subjects comprised 71 OC cases and 74 control women. Genotyping of TGF-β1 and IL-6 SNPs was done by real-time PCR. No differences were noted in the minor allele frequencies of the three TGF-β1 SNPs between OC patients and controls. However, marked differences in the distribution of TGF-β1 rs1800469 genotypes were seen between OC cases and controls (p < 0.001), with TGF-β1 rs1800469 heterozygous (C/T) genotype being negatively associated with OC (OR [95% CI] = 0.24 [0.15-0.58]). The allelic and genotypic distributions at IL-6 polymorphisms showed a positive association between minor allele (G) at IL-6 rs1880242 variant (p = 0.0275; R [95% CI] = 1.88 [1.03-3.46]) and the occurrence of OC. In fact, the presence of T allele [G/T + T/T] decrease the risk of OC (p = 0.021; OR [95% CI] = 0.38 [0.17-0.88]). In addition, the Haploview analysis demonstrated high linkage disequilibrium (LD) between IL-6 SNPs and eight-locus haplotype analysis identified that GGAGGGGA and GGAGGGTA haplotypes are positively associated with OC risk. A negative association was shown between IL-6 haplotype (TGGGCCTA) and OC occurrence.ConclusionsOur results suggest that TGF-β1 rs1800469, IL-6 rs1880242 variants and IL-6 haplotype (TGGGCCTA) have protective roles of OC risk. IL-6 haplotypes (GGAGGGGA and GGAGGGTA) increase OC susceptibility among Tunisian women.

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.

Prognostic value of interleukin-10 and tumor necrosis factor-\u03b1 polymorphisms in patients with hepatocellular carcinoma treated with transarterial chemoembolization

EnBackgroundTransarterial chemoembolization (TACE), a locoregional therapy, is widely recommended as first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). Several prognostic indices have been used to predict overall survival in HCC patients undergoing the procedure.Patients and methodsA total of 73 patients with HCC, candidate for TACE attending to HCC clinic, Specialized Medical Hospital, Mansoura University, were subjected to full history taking, physical examination, laboratory profile and testing for interleukin (IL)-10 and tumor necrosis factor (TNF)-α polymorphisms. Aggressiveness index is calculated for all patients and followed-up for 4 weeks after TACE to asses response. According to IL-10 and TNF-α polymorphisms results, patients were divided into groups and compared.ResultsThe aggressiveness index is significantly higher in the TT/AT haplotype of IL-10 and GG haplotype of TNF-α in comparison with the other haplotypes. The TT/AT haplotype of IL-10 and GG haplotype of TNF-α are significantly associated with less favorable outcome after TACE, wherein 64.3 and 56.25% of patients showed residual active tumor tissue, respectively.ConclusionThe TT/AT haplotype of IL-10 and GG haplotype of TNF-α are associated with more aggressive pattern of HCC and less favorable outcome after TACE; hence, these patients must be treated as early as possible.

Variation at Interleukin-10 Locus Represents Susceptibility to Psoriasis in North Indian Population.

IL-10 is an important pleiotropic, immunoregulatory and anti-inflammatory cytokine which plays a significant role in the pathogenesis of psoriasis. The aim of the present study was to determine whether the three polymorphic sites of the IL-10 gene, haplotype and serum level confer susceptibility to psoriasis. 200 psoriatic patients and 200 controls were genotyped for three IL-10 polymorphic sites by ARMS polymerase chain reaction. Serum levels of IL -10 were measured by ELISA. Our results demonstrated that polymorphism of IL-10 -592 C/A (adjusted* OR = 9.25; 95% CI =3.16- 27.06) and IL-10 1082 A/G (adjusted* OR = 4.28; (95% CI =1.46- 12.56) was found to be in association with increased risk of psoriasis while as IL- 10 819 C/T (adjusted* OR= 1.60; (95% CI = 0.65-3.95) polymorphism does not show any significant association with the risk of psoriasis. HT7 GTC haplotype is associated with increased risk of psoriasis. Serum levels of IL-10 were found to be significantly low in patients, as compared to controls with a non-significant correlation between serum IL-10 level and psoriasis severity. IL-10 polymorphism imparted significant risk towards the development of psoriasis in North Indian population. Highlighting the role of IL-10 cytokine in the pathogenesis of psoriasis will help in the development of psoriasis management.

Association between interleukin-10 polymorphisms and juvenile idiopathic arthritis: a meta-analysis

The aim of this review is to investigate IL-10 polymorphisms (-1082 G/A, -819 C/T, and -592 C/A) and their association with susceptibility to JIA. A meta-analysis was conducted after database search for relevant articles (MEDLINE and EMBASE). A total of seven studies involving 1495 patients and 1670 controls were considered in the meta-analysis. There was no association between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and JIA in allele contrast and any of the genetic models (allele contrast: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.79-1.02, P=0.09; OR=0.97, 95% CI 0.83-1.13, P=0.68; OR=0.92, 95% CI 0.81-1.06, P=0.24, respectively). In subgroup analysis, none of the subtypes of JIA including systemic, rheumatoid factor (RF)-positive polyarticular, RF-negative polyarticular, and oligoarticular was not significantly associated with IL-10 polymorphism. Meta-analysis of the IL-10 haplotype revealed no association between GCC, ACC, and ATA haplotypes and JIA. This meta-analysis showed that IL-10 polymorphisms were not associated with risk of JIA.

IL10 haplotypes are associated with diabetic nephropathy susceptibility in patients from western Mexico.

Diabetic Nephropathy (DN) is the main cause of chronic kidney disease (CKD) in diabetic patients. An IL-10 imbalance could be related to renal hypertrophy and trigger to nephropathy. Three promoter polymorphisms (-1082G>A, -819C>T, and -592C>A) at IL10 gene have been associated with changes in the IL-10 expression and DN susceptibility. Therefore, the aim of this study was to analyze this association in Mexican patients with DN. We conducted a case-control study on 128 patients with DN and 150 control subjects (CS) from western Mexico. All patients were tested for IL10 polymorphisms by PCR-RFLP. Allele frequencies, genotypes, and haplotypes were compared between groups. The significant haplotypes were correlated with patient clinical features. IL10 gene ATC haplotype (-1082A/-819T/-592C) was found significantly more frequent in DN patients than in CS (P<0.001; OR=3.6, 95% CI: 1.7-7.4). Similarly GTA (-1082G/-819T/-592A) haplotype was more frequent in DN patients than CS with significant differences (P<0.05; OR=4.02, 95% CI: 1.10-14.78). There were no correlations between IL10 haplotypes and clinical parameters in patients with DN. However, that there is a trend of higher serum urea levels and lower eGFR in ATC haplotype carriers compared to carriers of the other haplotypes (P<0.05). These results indicate that IL10 promoter haplotypes ATC and GTA carriers have a higher risk factor to develop DN in the western Mexican population.

Association of IL10 and TGFB single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population: a case control study

BackgroundConsidered as one of the major causes of low back pain, Intervertebral disc degeneration (IVDD) is caused by several genetic and environmental factors. As inflammation plays an important role in disc degeneration, the genetic changes in both inflammatory and anti-inflammatory genes may play causative roles in IVDD as well. Therefore, the interactions between inflammatory and anti-inflammatory cytokines and also other components of disc matrix would determine the degree of tissue destruction in disc degeneration. However, there is still controversy regarding the exact role of inflammation and disc homeostasis imbalance in pathophysiology of IVDD. Therefore, current study was conducted to investigate the role of IL-10 and TGF-β single nucleotide polymorphisms (SNP) in Iranian IVDD patients.MethodsSeventy-six IVDD patients and 140 healthy controls were enrolled in this study. Genomic DNA from peripheral leukocytes was tested for 3 SNPs in IL10 (L-10 -1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -592A/C (rs1800872)) and 2 SNPs in TGF-β (TGF-β Codon 10 C/T (rs1982037), and TGF-β Codon 25 C/T (rs1800471) genes through PCR-SSP method. The extracted genomic DNA was genotyped for the aforementioned SNPs of interest using specific primers, which were coated in the cytokines KITs and based on the PCR-SSP method for sequencing.ResultsThe ‘T’ allele of IL-10 -819C/T and the ‘C’ allele of IL-10 -592A/C were more prevalent among patients, whereas the ‘C’ and ‘A’ alleles of respective SNPs were significantly more frequent in controls. The genotypes including ‘CT’ of IL-10 -819C/T, ‘CA’ of IL-10 -592A/C, and ‘GA’ of IL-10 -1082A/G were more common among patients, while the ‘CC’ genotype of both IL-10 -819C/T and IL-10 -592A/C SNPs were more frequent in controls. In addition, the IL-10 haplotypes including ‘ACC’, ‘ATA’, and ‘ACA’ were significantly associated with disease. Meanwhile, the ‘TC’ haplotype of TGF-β was more common among patients as well.ConclusionsThe IL-10 SNPs were significantly associated with IVDD in Iranian population; which proposes that genomic alterations of anti-inflammatory cytokines could lead to homeostasis imbalance in intervertebral discs and degenerative changes.

Association of IL4, IL6, and IL10 polymorphisms with pulmonary tuberculosis in a Tibetan Chinese population.

BackgroundPulmonary tuberculosis (PTB) is an infectious disease with a high incidence worldwide. Genes encoding cytokines IL4, IL6, and IL10 are highly polymorphic and can influence the susceptibility to PTB.ResultsWe found correlations between one SNP in IL6 (rs2069837 p = 6.63E-11), seven SNPs in IL10 (rs1554286 p = 6.87E-20, rs1518111 p = 6.11E-11, rs3021094 p = 6.75E-29, rs3790622 p = 2.40E-06, rs3024490 p = 6.73E-11, rs1800872 p = 6.18E-11, rs1800871 p = 6.73E-11) and incidences of PTB. The SNPs rs2069837, rs1554286, rs1518111, rs3024490, rs1800872, and rs1800871 increased PTB risk by 1.95-fold, 2.34-fold, 1.84-fold, 1.84-fold, 1.84-fold and 1.84-fold, respectively. The SNPs rs3021094 and rs3790622 decreased PTB risk by 0.33-fold and 0.38-fold, respectively. We also found two linkage disequilibrium blocks in the studied IL SNPs. The IL4 haplotype TCCCGGA (OR = 1.33, p = 0.014) increased PTB risk, the IL10 haplotypes ATGGATA (OR = 0.39, p = 4.84E-06) provided a protective effect and decreased PTB risk.Materials and MethodsFor this study, we recruited 467 subjects with PTB and 503 healthy subjects from a Tibetan population living in Lhasa and nearby, China. Association analyses of sixteen single-nucleotide polymorphisms (SNPs) in IL4, IL6, and IL10 were performed.ConclusionsOur findings demonstrate an association between polymorphisms in IL6 and IL10 and risk of PTB.

Absolute quantification of Aggregatibacter actinomycetemcomitans in patients carrying haplotypes associated with susceptibility to chronic periodontitis: multifaceted evaluation with periodontitis covariants.

This study aimed to evaluate the association between haplotypes in the interleukin 8 (IL8) and IL4 genes previously associated to chronic periodontitis (CP) and the levels of Aggregatibacter actinomycetemcomitans (A.a.) in subgingival sites of patients with and without CP. Moreover, multifaceted evaluations were made to search associations among patients' genetic background with the A.a. levels and previous clinical/immunological/microbiological findings. Subgingival sites (n =596) of 104 patients were divided into susceptible to CP by the IL8 haplotype ATC/TTC (IL8+); non-susceptible to CP by the IL8 AGT/TTC (IL8-); susceptible to CP by the IL4 TCI/CCI (IL4+); protection against CP by the IL4 TTD/CTI (IL4-). Subgingival biofilm samples from diseased and healthy sites of CP patients and from control sites of health patients were obtained for absolute quantification of A.a. by quantitative real-time polymerase chain reaction. For diseased sites, samples were collected before and 45 days after periodontal treatment. The IL4 but not the IL8 haplotypes were associated with levels of A.a. (in both periods). After periodontal treatment, higher levels of A.a. were found in subgingival sites of (IL4-) patients, and higher levels of IL-4 were associated with deeper probing pockets in these same patients. Significant correlations were found among genetic (patients carrying IL8 or IL4 haplotypes), microbiological and immunological data showing the interrelationship of different factors in the CP.