Interleukin-10 Polymorphisms Research Articles

Common Polymorphisms of Interleukin-10 (-1082A/G, -592A/C, and -819C/T) in Oral Cancers: An Updated Meta-Analysis.

The mechanisms of genetic alteration are checked to be responsible for the oral cancer incidence. Herein, this meta-analysis aimed to assess the association between -1082A/G, -592A/C, and -819T/C polymorphisms of interleukin (IL)-10 and susceptibility to oral cancer. We systematically searched the PubMed, Web of Science, Cochrane Library, and Scopus databases until May 2019 to find the studies reporting the association between the IL-10 polymorphisms and the oral cancer risk. Rev Man 5.3 software was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). The CMA (version 2.0) software showed the results of publication bias. In addition, SPSS (version 22.0) was used for meta-regression analysis. Out of 8 studies included in this meta-analysis, 7, 6, and 5 studies reported -1082A/G, -592A/C, and -819T/C polymorphisms, respectively. The pooled ORs of the allele, homozygote, heterozygote, dominant, and recessive models were 1.64 (95% CI: 1.26-2.13), 2.99 (95% CI: 1.32-6.79), 1.64 (95% CI: 1.16-2.33), 1.77 (95% CI: 1.25-2.49), and 2.44 (95% CI: 1.21-4.92), respectively, showing a significant association for -1082A/G polymorphism, but not for -592A/C, and -819T/C polymorphisms with the risk of oral cancer. However, subgroup analysis showed an association for -592A/C polymorphisms, Caucasian ethnicity, and hospital-based controls. In summary, the findings of this meta-analysis illustrated an elevated risk of oral cancer related to -1082A/G polymorphism, but there was no association between -592A/C and -819C/T polymorphisms and the risk of oral cancer.

Association between Interleukin-10 Gene Polymorphisms and Behcet's Disease Susceptibility: Evidence from a Meta-Analysis.

Epidemiological studies have demonstrated that interleukin-10 (IL-10) polymorphisms may be associated with the development of Behcet's disease (BD). However, the published results were inconsistent. Therefore, this meta-analysis was conducted to derive a more precise relationship between IL-10 polymorphisms and BD susceptibility. Online databases (PubMed, Embase, Science Citation Index (SCI), CNKI, and WanFang) were searched to identify eligible studies. Odds ratio (OR) and a 95% confidence interval (CI) were applied to assess the relationship strength between IL-10 -1082A>G (rs1800896), -819T>C (rs1800871), and -592A>C (rs1800872) polymorphisms and BD susceptibility. Publication bias, sensitivity, and cumulative analyses were conducted to measure the robustness of our findings. Finally, fifteen articles (36 independent case-control studies) involving 5,971 patients and 8,913 controls were included. Overall, significant associations between -819T>C polymorphisms and BD risk were observed in the total population (C vs. T: OR = 0.72, 95%CI = 0.67‐0.77, P < 0.01, I2 = 36.6%; TC vs. TT: OR = 0.73, 95%CI = 0.66‐0.80, P < 0.01, I2 = 23.0%; CC vs. TT: OR = 0.52, 95%CI = 0.39‐0.70, P < 0.01, I2 = 53.7%; TC+CC vs. TT: OR = 0.67, 95%CI = 0.61‐0.71, P < 0.01, I2 = 22.1%; and CC vs. TT+TC: OR = 0.66, 95%CI = 0.53‐0.82, P < 0.01, I2 = 57.8%). Moreover, the IL-10 -592 A>C polymorphism and the ACC haplotype exhibited a significant, protective effect against BD susceptibility. In summary, our meta-analysis suggested that IL-10 gene polymorphisms may play a salient role for BD development.

Impact of IL-17F 7488T/C Functional Polymorphism on Progressive Rheumatoid Arthritis: Novel Insight from the Molecular Dynamic Simulations

ABSTRACT Resorption of bones and cartilage coupled with structural changes in the inflamed joints are the major hallmark of rheumatoid arthritis (RA). Genetic polymorphisms in pro-inflammatory interleukins (ILs) appear to play an important role in the susceptibility towards progressive RA. We therefore aimed to investigate the association of single nucleotide polymorphisms (SNP), present in the hotspot coding/promoter regions of IL-6, −17 and −18, with RA susceptibility or severity in a larger study cohort from Pakistan together with finding clues as to how a functional SNP impacts the predisposition towards RA. TaqMan SNP genotyping approach was first used to assess IL-6 (rs1800795), IL-17 F (rs763780), IL-17A (rs2275913), and IL-18 (rs1946518) polymorphisms in 310 subjects (150 RA and 160 control). Molecular dynamic simulations (MDS) of wild- and mutant-type IL-17A with corresponding receptor were thereafter performed using AMBER-16; Chimera 1.13 was used for analyses. Our results showed the association of two SNPs, namely IL-6 − 174 G/C [allelic (OR = 0.960, 95% CI = 0.929–0.992, p = .009)] and IL-17 F 7488 T/C [allelic (OR = 0.907, 95%CI = 0.861–0.954, p = .000)] with increased RA risk in Pakistani subjects. When mapped, IL-17 F 7488 T/C was found involved in His161→Arg161 change near the C-terminus of IL-17 F. Comparative MDS revealed enhanced stability of the mutant hence advocating a potential role of IL-17F functional SNP in RA susceptibility and/or severity. This study provides a novel structural insight for SNP-derived functional mutation and its overall impact on binding with heterotrimeric receptor complex of IL-17 receptor thereby opening new avenues for understanding the biochemical basis of the disease.

Associations of IL-18 and IL-9 expressions and gene polymorphisms with asthma.

To explore the associations of interleukin-18 (IL-18) and IL-9 gene polymorphisms with susceptibility to asthma, and to study the associations between IL-18 and IL-9 expression levels and polymorphisms. A total of 200 asthma patients in our hospital were collected as disease group, while 200 healthy people were taken as control group. The deoxyribonucleic acid (DNA) was extracted from peripheral blood and sent to the company for the detection of IL-18 and IL-9 gene polymorphisms via sequencing. The levels of serum IL-18 and IL-9 were determined using enzyme-linked immunosorbent assay (ELISA), and arterial blood gas analysis was performed for patients. The allele distributions at IL-18 gene loci rs189667 and rs360715 had no differences between control group and disease group. The allele distributions at IL-9 gene loci rs1859430 and rs2066758 were different between the two groups (p=0.001, p=0.022), among which the G allele frequency was the highest in disease group [245 (0.613)], and the T allele frequency was also the highest in disease group [240 (0.600)]. There was a difference in the genotype distribution at IL-9 gene locus rs1859430 between the two groups, and the GG genotype frequency in disease group [82 (0.410)] was significantly higher than that in control group (p=0.005). The CC genotype frequency at rs2066758 was significantly lower in disease group [27 (0.135), p=0.044]. In disease group, the frequency of heterozygous model CT (p=0.047) at IL-18 gene locus rs360715, and recessive model GA+AA (p=0.021) and heterozygous model GA (p=0.031) at IL-19 gene locus rs1859430 was significantly lower than that in control group. In disease group, the AC haplotype frequency at IL-18 gene loci rs189667 and rs360715 was evidently lower than that in control group (p=0.048). Disease group had evidently lower AT haplotype frequency (p=0.006) and evidently higher GT haplotype frequency (p=0.000) at IL-9 gene loci rs1859430 and rs2066758. Moreover, the level of serum IL-18 in patients with TT genotype at IL-18 gene locus rs360715 was higher than that in those with other genotypes in disease group (p<0.05), and the level of serum IL-9 in patients with AG genotype at IL-9 gene locus rs1859430 was also higher than that in those with other genotypes in disease group (p<0.05). There was a remarkable association between CT genotype at IL-18 gene locus rs360715 and partial pressure of oxygen (PaO2) (p=0.035), and between CC genotype at IL-9 gene locus rs2066758 and partial pressure of carbon dioxide (PaCO2) (p=0.041). The expression levels of serum IL-18 and IL-9 and their gene polymorphisms are significantly associated with asthma.

P1570INTERLEUKIN-6 (RS1800795) AND PENTRAXIN 3 (RS2305619) GENETIC POLYMORPHISMS AND THEIR RELATION WITH INFLAMMATION AND ALL-CAUSE MORTALITY IN ESRD PATIENTS ON DIALYSIS

Abstract Background and Aims Chronic inflammation plays an important role in progression and outcome of chronic kidney disease (CKD) patients. The interleukin-6 (IL-6) polymorphism, rs1800795, is a single nucleotide polymorphism (SNP) in the promoter region (-174G/C) that regulates gene transcription and affects the levels of this cytokine. Genetic variants in the promotor region have been associated with a poor outcome in several pathologies, namely in coronary artery disease. Pentraxin 3 (PTX3) is an inflammatory protein, produced locally by different cell types (e.g. mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells). PTX3 polymorphism, rs2305619, is a SNP (+281A&amp;gt;G) in the intron 1 of PTX3 gene. PTX3 polymorphisms have been described as risk factor for development of coronary artery disease and for an impairment of kidney function. Our aim was to determine the allelic frequencies of IL6 and PTX3 in end-stage renal disease (ESRD) patients and controls, as well as their relationship with the inflammatory response. Method We studied 289 ESRD patients on hemodialysis (high-flux hemodialysis or hemodiafiltration) and 22 healthy individuals, matched for gender, body mass index, and, as far as possible, for age. Real-Time PCR TaqMan SNP genotyping assays were used to assess allelic frequencies of IL6 (rs1800795) and PTX3 (rs2305619). We evaluated the circulating levels of PTX3, growth differentiation factor (GDF)-15, high-sensitivity C-reactive protein (hsCRP), IL-6, tumor necrosis factor-alpha (TNF-α), soluble TNF receptor 2 (sTNFR2), hepcidin and transferrin, using commercially available kits. Deaths occurring along 1-year follow-up period were recorded and mortality rates were evaluated for homozygous and heterozygous alleles. Results Compared to controls, all inflammatory biomarkers were significantly higher in ESRD patients. Allelic frequencies in ESRD patients and controls were similar for both SNPs, IL-6 -174G/C and PTX3 +281A&amp;gt;G, considering the homozygous and the heterozygous alleles. For the IL-6 -174G/C, the CC patients, compared to GG and heterozygous patients, showed significantly higher GDF-15 and CRP concentrations and significantly lower values of transferrin; moreover, we found that CC patients presented a trend towards higher mortality rate (21%, 10% and 7% for CC, GG and GC, respectively; P=0.072). For PTX3 +281A&amp;gt;G polymorphism, the AA patients, compared to GG and heterozygous patients, presented higher hsCRP; no significant differences were found in mortality rate between different allele carrier groups (P=0.703). Conclusion Although no differences were found in the allelic frequencies between controls and ERSD patients, the CC patients for IL6 polymorphism (rs1800795) and AA patients for PTX3 polymorphism (rs2305619), showed an enhanced inflammatory response; the association of the IL6 polymorphism with a higher mortality needs further studies.

Gene polymorphisms of pro-inflammatory cytokines may affect the risk of Graves' disease: a meta-analysis.

Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves' disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves' disease by pooling the findings of all relevant studies. A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves' disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects in Asians also differed significantly. Nevertheless, we did not detect such genotypic frequencies differences for TNF-α rs361525 and IL-1B rs1143627 polymorphisms. This meta-analysis suggests that TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in overall population. Moreover, TNF-α rs1800629 and IL-6 rs1800795 polymorphisms may influence the risk of Graves' disease in Caucasians, while IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in Asians.

IL-6, IL-8 and IL-10 polymorphisms may impact predisposition of Alzheimer's disease: a meta-analysis.

Gene polymorphisms in interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) may affect the predisposition of Alzheimer's disease (AD), but the results of the so far published studies remain controversial. The authors conducted this meta-analysis to assess relationships between IL-6/IL-8/IL-10 polymorphisms and predisposition of AD by pooling the findings of so far published studies. A comprehensive search of Pubmed, Embase, Web of Science, and CNKI was endorsed by the authors to identify the already published studies. Forty-five studies were found to be eligible for meta-analyses. The pooled meta-analyses results showed that genotypic frequencies of IL-6 -174 G/C, IL-6 -572 G/C and IL-10 -1082 A/G polymorphisms among patients with AD and controls differed significantly. Moreover, genotypic frequencies of IL-6 -174 G/C, IL-6 -572 G/C, and IL-8 -251 A/T polymorphisms among patients with AD and controls in Asians also differed significantly. But no such genotypic frequencies' differences were observed for IL-10 -819 C/T and 592 C/A polymorphisms. This meta-analysis suggests that IL-6 -174 G/C, IL-6 -572 G/C, and IL-10 -1082 A/G polymorphisms may affect the predisposition of AD in overall population. Moreover, IL-6 -174 G/C, IL-6 -572 G/C, and IL-8 -251 A/T polymorphisms may affect the predisposition of AD in Asians.

Interleukin-1\u03b2 and interleukin-6 gene polymorphisms in Egyptian sickle cell disease patients

BackgroundSickle cell disease (SCD) is a disorder characterized by a heterogeneous clinical outcome. Interleukin-1β (IL-1β) and interleukin-6 (IL-6) are important mediators of inflammatory response. Genetic modifiers that alter cytokine levels may contribute to the clinical variability of SCD. The present study investigated the associations of IL-1β + 3954 C>T and IL-6 (− 174G>C and − 597 G>A) gene polymorphisms with clinical and laboratory data in SCD patients. The study was conducted on 100 SCD patients (59 sickle cell anemia patients “SS” and 41 sickle beta thalassemia patients “Sβ”). Fifty age- and sex-matched healthy volunteers were included as a control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for the detection of IL-1β and IL-6 gene polymorphisms.ResultsThe homomutant genotypes of IL-1β (+ 3954 C>T), IL-6 (− 174G>C), and IL-6 (− 597 G>A) were infrequently presented among SCD patients and control group. No significant differences were detected between SS, Sβ patients, and control group as regards the genotypic frequencies and allele distributions of the studied polymorphisms. As regards the clinical complications, the mutant genotypes of IL-1β (+ 3954 C>T) had a significantly higher frequency among Sβ patients with splenomegaly. Hemoglobin is significantly lower in SS patients with mutant allele (AA and GA) for IL-6 (− 597 G>A) (P = 0.005), while Sβ patients with mutant genotype for IL-6 (− 597 G>A) had significantly higher total leucocytic count (P = 0.031).ConclusionIL-1β (+ 3954 C>T), IL-6 (− 174G>C), and IL-6 (− 597G>A) polymorphisms are not associated with disease phenotype. However, IL6 polymorphism (− 597 G>A) might predispose to underlying inflammatory process.

The effect of interleukin 10 polymorphisms on breast cancer susceptibility in Han women in Shaanxi Province.

Previous studies have reported on several genetic variants related to breast cancer, but a substantial proportion of mutation loci have not yet been identified. In the current study, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10) and susceptibility to breast cancer in Shaanxi Han women in China. Six SNPs were genotyped in 530 breast cancer patients and 628 healthy women from the First Affiliated Hospital of Xi'an Jiaotong University Hospital. Odds ratios and 95% confidence intervals were calculated by unconditional logistic regression analysis to assess the association between breast cancer risk and polymorphisms of six loci. Two SNPs, rs3024490 and rs1800871, were found to be significantly different between breast cancer patients and healthy women. These SNPs also increased the risk of breast cancer in co-dominant and dominant models. Moreover, another SNP, rs1554286, was significantly associated with an increased risk of breast cancer in the co-dominant model. Functional assessments indicated that these three variants may influence the expression and transcription factor binding of IL-10. Our findings suggest that variants of IL-10 may be likelihood risk factors for the development and progression of breast cancer. Future studies should replicate this study and evaluate functional assessments in Chinese Han women and women from other regions.

Effects of gene polymorphism and serum levels of IL-2 and IL-6 on endometriosis.

EMT is closely related to gene polymorphism and the expression level of immune-related substances in patients. Therefore, the aim of this study was to investigate the relationship between single nucleotide polymorphism (SNP), as well as serum levels of interleukin 2 (IL-2) and interleukin 6 (IL-6) in patients with endometriosis (EMT) and disease susceptibility. Peripheral blood of EMT patients and healthy people were collected, respectively. Genomic deoxyribonucleic acid (DNA) was extracted and sequenced to obtain gene polymorphisms of IL-2 rs11575812 (T>C), rs2069772 (A>G), rs2069762 (T>G), and IL-6 rs1800795 (C>G). Meanwhile, the serum levels of IL-2 and IL-6 were determined by the relative kits. For IL-2 rs11575812 allele (C>G), the odds ratio (OR) was 0.49, the 95% confidence interval (CI) was 0.37-0.66, and the p-value was 0. For IL-2 rs2069772 allele (C>G), the OR was 0.97, the 95% CI was 0.73-1.27, and the p-value was 0.83. For IL-2 rs2069762 allele (T>G), the OR was 1.73, the 95% CI was 1.31-2.29, and the p-value was 0. For IL-6 rs1800795 allele (C>G), the OR was 1.26, the 95% CI was 0.96-1.66, and the p-value was 0.09. CC genotype (p=0.000) and TT genotype (p=0.040) of IL-2 rs11575812 (T>C), AG genotype (p=0.000) of IL-2 rs2069772 (A>G), and GT genotype (p=0.000) of rs2069762 (T>G) were remarkably associated with the serum level of IL-2 in patients with EMT. Similarly, the CG genotype (p=0.000) of IL-6 rs1800795 (C>G) was significantly correlated with the serum level of IL-6 in patients with EMT. IL-2 haplotype CAG (p=0.005), CAT (p=0.001), CGG (p=0.047), TAG (p=0.000), and TGG (p=0.000) were significantly different from other haplotypes. Furthermore, there was a significant correlation between the serum levels of IL-2 and IL-6 (r=0.63, p<0.001). IL-2 rs11575812 (T>C) TT genotype, rs2069772 (A>G) AG genotype and rs2069762 (T>G) GG genotype increases the risk of EMT, which are related to the serum levels of IL-2 and IL-6.

Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus.

BACKGROUNDChronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.AIMTo investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients.METHODSTwo hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models.RESULTSType 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls (P = 0.81) and all alleles were in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001).CONCLUSIONThis study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.

Genetic polymorphisms of interleukin-6 influence the development of hepatitis B virus-related liver cirrhosis in the Han Chinese population

BackgroundInterleukin-6 (IL-6) plays an important role in chronic inflammation. Thus, we aimed to investigate the effects of IL-6 polymorphisms on predicting the progression of hepatitis B virus (HBV)-r elated liver cirrhosis. MethodsA cross-sectional study was conducted to analyse IL-6 polymorphisms and serum levels of IL-6 in HBV-infected patients at different clinical phases and in healthy controls. IL-6 polymorphisms were detected by the TaqMan PCR method, and plasma IL-6 levels were assessed by ELISA. ResultsOur analysis included 182 chronic hepatitis B (CHB) patients, 190 HBV-infected liver cirrhosis cases, 125 inactive HBsAg carriers, and 246 healthy controls. Seven SNPs in IL-6 including rs10499563, rs17147230, rs1800796, rs2069837, rs1524107, rs2066992, and rs2069852 were analysed. In a haplotype analysis between HBV-infected liver cirrhosis cases and CHB patients, inactive HBV carriers or healthy controls, haplotype CT in block 1 and haplotype GGCGG in block 2 were associated with liver cirrhosis (P <0.05). Moreover, the genotype or allele frequencies were significantly different in IL-6 rs10499563 and rs2069837 when HBV-infected liver cirrhosis patients were compared with CHB patients, inactive HBV carriers or healthy controls. A further study found that compared with that in the healthy controls, inactive HBV carriers or CHB patients, plasma IL-6 was elevated in HBV-infected liver cirrhosis patients. ConclusionIn conclusion, the IL-6 rs10499563 and rs2069837 polymorphisms are associated with incidence of liver cirrhosis may through their effects on IL-6 expression and these two single nucleotide polymorphisms can be used as potential prognostic markers of HBV-related liver cirrhosis.

Association of IL-4 Polymorphisms with Allergic Rhinitis in Jordanian Population.

Background and objectives: Allergic rhinitis has complex patterns of inheritance, and single nucleotide polymorphisms, a common genetic variation in a population, exert a significant role in allergic rhinitis pathology. The current study aimed to investigate the association of Interleukin-4 (IL-4) polymorphisms with allergic rhinitis. Materials and Methods: Our study included 158 patients with allergic rhinitis and 140 healthy controls from Jordan that were genotyped for IL-4 single nucleotide polymorphisms (SNPs) C-589T (rs2243250) and T-2979G (rs2227284) using restriction fragment length polymorphism-polymerase chain reaction. Statistical analysis was conducted using IBM SPSS Statistics version 24 software. Results: The results showed that the allelic frequency of the minor alleles was 0.19 and 0.67 for C-589T (rs2243250) and T-2979G (rs2227284) in the allergic rhinitis patients, respectively, while it was 0.18 for C-589T (rs2243250) and 0.64 T-2979G (rs2227284) in the control group. The homozygous (TT) genotype of C-589T (rs2243250) was significantly associated with allergic rhinitis (p < 0.05), while there was no association of any of T-2979G (rs2227284) genotypes with allergic rhinitis. Conclusions: The results of this study indicate that genetic inter-population variation precipitates the differences in the percentages of many diseases among populations, including allergic rhinitis.

In silico prediction of deleterious single nucleotide polymorphisms in human interleukin 27 (IL-27) gene

Single-nucleotide polymorphisms (SNPs) associated studies are particularly useful to identify disease-related genetic variations. However, large amount of SNPs are a major challenge for the analysis of human genetic variations and potential pathogenic mutations detection. Computational prediction tools have a great potential to sort out the possible functional SNPs. In the present study, for the first time, deleterious single nucleotide polymorphisms were investigated in human interleukin 27 (IL-27) gene by using different bioinformatics predictive tools. To this aim only conserved and validated SNPs with minor allele frequency (MAF) > 0.01 (a total of 114 SNPs) were subjected to further analysis. The nonsynonymous SNPs (nsSNPs) were analyzed by SIFT, PolyPhen, PROVEAN, SNP&GO, MutPred, INPS, and I-Mutant tools. The Non-coding SNPs (ncSNPs) were also analyzed by SNPinfo and RegulomeDB tools. In our in silico analysis, we predicted 2 nsSNPs and 20 ncSNPs as potential candidates in the IL-27 gene, which could be a priority for future case-control studies.

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis.

Background: non-alcoholic steatohepatitis (NASH) recently headlined hepatocellular carcinoma (HCC) worldwide. This study aims to unveil the role of some unaddressed critical players that might aid in understanding, predicting, and targeting NASH and NASH-HCC. Methods: Serum interleukin 13 (IL-13) levels and single nucleotide polymorphisms (SNPs) within interleukin (IL)-13 rs20541, IL-13 receptors (IL-13R1) rs2248841, (IL-13R2) rs5946040, signal transducer activator of transcription 6 (STAT6) rs167769, yes-associated protein (YAP1) rs11225163, programmed death-ligand 1 (PD-L1) rs2282055, and programmed death-ligand 2 (PD-L2) rs7854413 genes were analyzed by qRT-PCR. Multiple stepwise regression analysis was performed on a cohort of 134 Egyptian male patients diagnosed with NASH and NASH-HCC. RESULTS: higher serum alpha-fetoprotein (AFP) and higher serum IL-13 levels were directly associated with HCC development in NASH (odds ratio (OR) 19.6 and 1.9 p < 0.01). Reversibly, the presence of the C/C genotype in STAT6 rs167769 and the C allele carrier YAP1 rs11225163 were inversely associated with HCC in NASH patients (OR 0.015 and 0.047 p < 0.01). A predictive model was formulated with 97.5% specificity, 90.9% sensitivity, and 94.8% accuracy. Moreover, higher serum IL-13 levels and the presence of PD-L2 rs7854413 C allele carriers were associated with advanced fibrosis progression in NASH patients (OR 1.432 and 3.797 p < 0.01). Serum levels of IL-13 and C/C genotype in STAT6 rs167769 significantly increased the predictive capacity of serum AFP to predict HCC in F1–F2 and in F3–F4 fibrosis grades NASH patients. Conclusion: association between serum IL-13 and PD-L2 rs7854413 polymorphism successfully predict advanced fibrosis in NASH. However, HCC development in NASH is associated with higher serum AFP, IL-13 levels, and STAT6 rs167769, YAP1 rs11225163 polymorphisms.

Interleukin-6 polymorphisms in HCC patients chronically infected with HCV

Hepatocellular carcinoma is a primary liver malignancy in which the risk of development is always multifunctional. Interleukin-6 is a proinflammatory and multifunctional cytokine, which plays an important role in the immune response, haematopoiesis and defence against viral infection. We aimed to evaluate the frequency of Interleukin-6 mutations (rs2069837 and rs17147230) associated with genetic risk of hepatocellular carcinoma in Khyber Pakthunkhwa population. A total of 72 hepatocellular carcinoma cases and 38 controls were included in this study. The genomic DNA was extracted from the peripheral blood cells and Interleukin-6 genotyping was performed using T-ARMS-PCR technique. Our results show a significant increase risk of developing hepatocellular carcinoma with the mutation within Interleukin-6 gene with heterozygous G allele (rs2069837) (OR = 10.667, 95%CI = 3.923–29.001, p = < 0.0001) and heterozygous T allele (rs17147230) (OR = 75.385, 95%CI = 9.797–580.065, p = < 0.0001). However, under recessive gene model the results were insignificant in case of Interleukin-6 rs2069837 (OR = 0.605, 95%CI = 0.217–1.689, p = 0.337), while significant in case of Interleukin-6 rs17147230 (OR = 0.298, 95%CI = 0.121–0.734, p = 0.0085). In conclusion, Interleukin-6 mutation is associated with hepatocellular carcinoma susceptibility. More related studies with other associated interleukins and their whole gene sequencing will be required.

Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients.

Single nucleotide polymorphisms in cytokine genes including interleukin-10 have been described to play a vital role in the overall pathogenesis of systemic lupus erythematosus. However, due to a lack of evidence from the Indian population, this study was conducted to analyse the possible influence of interleukin-10 promoter polymorphisms over the disease susceptibility, serum interleukin-10 level and clinical manifestations of the disease in Indian systemic lupus erythematosus patients. In total, 200 systemic lupus erythematosus patients and 201 controls were recruited under this study. Genotyping of interleukin-10 (−1082A/G; −819T/C and −592C/A) polymorphisms was done by direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods respectively. Serum interleukin-10 levels were measured by multiplex assay. Interleukin-10 −1082G and −592A allele frequencies were significantly increased in systemic lupus erythematosus patients (corrected p value &lt;0.05). Also, combined −1082AG+GG, −819TC+CC and −592CA+AA genotype frequencies were significantly increased in the patient group. A higher trend of association between −1082AG+GG genotype frequency was observed in patients with serositis (odds ratio = 2.7, p = 0.0233, corrected p value = 0.2097). Serum interleukin-10 levels were significantly higher in systemic lupus erythematosus patients (4.3 ± 3.1 pg/ml) than controls (2.6 ± 1.4 pg/ml) ( p &lt; 0.0001). Furthermore, interleukin-10 levels were positively correlated with disease activity ( p = 0.39, p &lt; 0.0001). The frequency of the GCA (−1082, −819, −592) haplotype was significantly higher in systemic lupus erythematosus patients (10.6%) than controls (1.6%) (odds ratio = 5.4, p = 0.0330). Moreover, ACC, GCC and GCA haplotypes were found to be strongly associated with serositis. However, the frequency of the ACC haplotype was significantly higher in patients with neurologic involvement (odds ratio = 14.9, corrected p value &lt;0.001). Thus, interleukin-10 promoter polymorphisms suggest they have a proactive role in increased susceptibility to the disease among Indian systemic lupus erythematosus patients.

IL-10, IL-18 Gene Polymorphisms Might Influence Predisposition to Coronary Artery Disease in East Asians: A Meta-Analysis

ABSTRACT The results of already published studies regarding relationship between interleukin-10 (IL-10), interleukin-18 (IL-18) polymorphisms and predisposition to coronary artery disease (CAD) were still controversial. So the authors designed this meta-analysis to more precisely estimate relationship between IL-10, IL-18 polymorphisms and CAD by pooling the results of already published studies. The authors searched Pubmed, Embase, Web of Science and CNKI for already published studies. The authors used Review Manager to pool the results of already published studies. Thirty-four studies were pooled analyzed in this meta-analysis. The pooled meta-analyses results showed that IL-18 rs187238, IL-18 rs1946518 and IL-18 rs1946519 polymorphisms were all significantly associated with predisposition to CAD in the general population. We also detected similar significant results for IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms in East Asians in further subgroup analyses. In conclusion, this meta-analysis suggested that IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms might influence predisposition to CAD in East Asians.

Associations of polymorphisms in interleukins with susceptibility to breast cancer: Evidence from a meta-analysis

BackgroundAssociations between polymorphisms in interleukins and breast cancer (BC) were already investigated by many studies, yet with controversial findings. The aim of this meta-analysis was to better clarify associations between polymorphisms in interleukins and BC by combing the results of all relevant articles. MethodsEligible articles were searched from Pubmed, Embase, Web of Science and CNKI. We used Review Manager to combine the results of eligible studies. ResultsFifty-seven studies were included in this meta-analysis. We found that IL-6 rs1800796 (dominant comparison: OR = 0.70, 95% CI 0.53–0.92), IL-8 rs4073 (dominant comparison: OR = 0.74, 95% CI 0.61–0.89; over-dominant comparison: OR = 1.16, 95% CI 1.05–1.29; allele comparison: OR = 0.82, 95% CI 0.69–0.89), IL-10 rs1800896 (recessive comparison: OR = 1.28, 95% CI 1.12–1.47) and IL-18 rs1946518 (dominant comparison: OR = 0.80, 95% CI 0.65–0.97; allele comparison: OR = 0.74, 95% CI 0.59–0.93) polymorphisms were all significantly associated with BC in overall combined analyses. In subgroup analyses, we noticed that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800896, IL-18 rs1946518 and rs187238 polymorphisms were all significantly associated with susceptibility to BC in East Asians from China. ConclusionsCollectively, this meta-analysis demonstrated that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800896, IL-18 rs1946518 and rs187238 polymorphisms may confer susceptibility to BC for East Asians from China.

Cytotoxin-associated gene-A-seropositivity and Interleukin-1 polymorphisms influence adverse cardiovascular events

AimsAlthough the bacterial virulent factor of cytotoxin-associated gene-A (CagA)-seropositivity and the host genetic factors of interleukin (IL)-1 polymorphisms have been suggested to influence Helicobacter pylori (HP) -related diseases, the underlying mechanisms of the association between HP infection and acute coronary syndrome (ACS) remain unknown. Methods and resultsAmong 341 consecutive ACS patients, the clinical outcomes after ACS included composite cardiovascular events within the 2-year follow-up period.A significantly higher probability of primary outcomes was observed in HP positive patients than in HP negative patients. There were no significant differences in the rate of cardiovascular events between HP positive and HP negative patients in the absence of an IL-polymorphism, while there were significant differences in the presence of an IL-polymorphism. There were significant differences in the rate of cardiovascular events among CagA positive, CagA negative/ HP positive and CagA negative/HP negative patients. Moreover, via immunohistochemical staining, aortic CagA positive cells were confirmed in the vasa vasorum in CagA positive patients, whereas they could not be identified in CagA negative patients. ConclusionsThe bacterial virulence factor CagA and host genetic IL-1 polymorphisms influence the incidence of adverse cardiovascular events, possibly through infection of atherosclerotic lesions.Registration: University Hospital Medical Information Network (UMIN)-CTR (http://www.umin.ac.jp/ctr/).Identifier: UMIN000035696.