IL-10 Single Nucleotide Polymorphisms Research Articles

Association of a PD-L2 Gene Polymorphism with Chronic Lymphatic Filariasis in a South Indian Cohort.

Lymphatic filariasis (LF) is a parasitic infection, caused by three closely related nematodes, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. Previously, we have shown that lysate from B. malayi microfilariae induces the expression of interleukin (IL)-10 and programmed death-ligand (PD-L) 1 on monocytes, which lead to inhibition of CD4+ T-cell responses. In this study, we investigated associations of IL-10 and programmed cell death (PD)-1 pathway gene polymorphisms with clinical manifestation in LF. We evaluated the frequency of alleles and genotypes of IL-10 (rs3024496, rs1800872), IL-10RA (rs3135932), IL-10RB (rs2834167), PD-1 (rs2227982, rs10204525), PD-L1 (rs4143815), PD-L2 (rs7854413), and single-nucleotide polymorphisms (SNPs) in 103 patients with chronic pathology (CP), such as elephantiasis or hydrocele and 106 endemic normal (EN) individuals from a South Indian population living in an area endemic for LF. Deviations from the Hardy-Weinberg equilibrium were tested, and we found a significant difference between the frequency of polymorphisms in PD-L2 (rs7854413; P < 0.001) and IL-10RB (rs2834167; P = 0.012) between the CP and the EN group, whereas there were no significant differences found among IL-10, IL-10RA, PD-1, and PD-L1 SNPs. A multivariate analysis showed that the existence of a CC genotype in PD-L2 SNP rs7854413 is associated with a higher risk of developing CP (OR: 2.942; 95% confidence interval [CI]: 0.957-9.046; P = 0.06). Altogether, these data indicate that a genetically determined individual difference in a non-synonymous missense SNP of PD-L2 might influence the susceptibility to CP.

Evaluation of Polymorphisms in IL8 and IL16 Genes in Patients with Acute Coronary Syndrome

Abstract Background: Acute coronary syndrome (ACS) is a cardiovascular disease caused by obstruction of coronary arteries by atheromatous plaque. Susceptibility to this disease may be related to genetic variations, such as single nucleotide polymorphisms (SNPs). Objective: In this study, we evaluated the relationship between SNPs in IL8 (rs4073; -251 A/T) and IL16 (rs11556218; T/G) genes and SCA in a Brazilian population. Materials and Methods: A sample of 200 patients with ACS and 50 non-ACS patients hospitalized at the Real Hospital Portugues, Recife - PE, Brazil, and 220 blood donors (donors) was used. Genotyping was carried out by polymerase chain reaction, and DNA sequencing. Statistical analyzes were performed using the Williams G, Chi-square and Kruskal Wallis tests, using the BioEstat 5.0 program, and the data with a value of p 0.05) in all three groups. In the IL16 gene, genotypic distributions were different between patients with ACS and the donor group (p = 0.002), with the most frequent G allele in the second group (p = 0.0052). The IL-16 cytokine was higher in donors than in patients with ACS (p = 0.04) and the G (TG + GG) allele had higher values of this cytokine (p = 0.01). Conclusions: The results demonstrate the important role of the rs11556218 SNP in IL16 gene in SCA, evidencing that the G allele may be associated with a decreased risk of the disease.

Preliminary analysis of single-nucleotide polymorphisms in IL-10, IL-4, and IL-4R\u03b1 genes and profile of circulating cytokines in patients with gastric Cancer

BackgroundGastric Cancer is highly prevalent and deadly worldwide. In Colombia, it is the most lethal form of cancer. Some single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Rα genes have been associated with an anti-inflammatory environment and a Th2 profile in detriment of the antitumor Th1 response. This research sought to detect single-nucleotide polymorphisms in promoter sequences, like − 1082 (G/A), − 592 (C/A), and − 819 (C/T), as well as − 590 (C/T) of the IL-10 and IL-4 genes, respectively; in addition to the IL-4Rα mutation variants, Ile50Val and Q576R, together with circulating levels of IL-4, TNF-α, IL-10, and IFN-γ in patients with gastric carcinoma in Cúcuta, Colombia.MethodsIn a cross-sectional study, 17 patients and 30 healthy individuals were genotyped for the six polymorphisms mentioned through PCR-RFLP of DNA obtained from peripheral blood cells and serum samples were analyzed by sandwich ELISA to quantify cytokines. Statistical difference between groups was determined along with the association between the presence of polymorphisms and the risk of gastric cancer, as well as the mortality in patients, using Mann-Whitney U test and logistic regression analysis, respectively.ResultsAn association between the − 1082 (G/A) and the risk of gastric cancer was found (OR = 7.58, range 0.77–74.06, P = 0.08). Furthermore, patients had a significant increase in IL-4 serum levels (P < 0.01) compared to healthy individuals, both variables showed a higher estimated risk of mortality in patients, although without statistical association (P > 0.05).ConclusionWe infer that two possible biomarkers (one immunological and one genetic) could be considered in association with gastric cancer in our population, which should be confirmed by subsequent studies involving a greater number of individuals.

Genetic polymorphisms in interleukin 13 gene with the susceptibility to nasopharyngeal carcinoma in a Chinese population

Although inflammation is emerging as a candidate risk factor in tumorigenesis of nasopharyngeal carcinoma (NPC). In particular, Interleukin (IL) 13 involved inflammatory diseases and cancers. Single nucleotide polymorphisms in IL-13 have been associated with multiple cancers. The study analyzed genetic polymorphisms in IL-13 aiming to investigate its’ potential susceptibility with the NPC. The genotyping of polymorphisms (rs20541, rs1295687 and rs2069744) was examined by Snapshot SNP and DNA sequencing. All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in NPC and controls. Adjusted logistic regression showed that the TT genotype of rs20541 increased the risk of lymph node metastasis (TT vs. CC: OR = 2.87, 95%CI, 1.33–6.18, P = 0.007). CT/CC genotypes were associated with the decreased the risk of lymph node metastasis in NPC (CT/CC vs. TT: OR = 0.32, 95%CI, 0.16–0.65, P = 0.002). The concentration of IL-13 was significantly elevated in NPC patients compared with controls (P = 0.012). Moreover, significant differences were detected in the T-C-T haplotype distribution between NPC patients and controls (OR = 2.47, 95%CI, 1.06–5.78, P = 0.031). Our results, the first report, provide evidence that rs20541 polymorphisms may affect the lymph node metastasis of NPC patients in Chinese population.

Association of IL-10 and IL-10RA single nucleotide polymorphisms with the responsiveness to HBV vaccination in Chinese infants of HBsAg(+)/HBeAg(−) mothers: a nested case–control study

ObjectivesTo investigate the association of interleukin (IL)-10 and IL-10 receptor A (IL-10RA) single nucleotide polymorphisms with the responsiveness to hepatitis B virus (HBV) vaccination in newborns whose mothers were hepatitis...

Gene expression and six single nucleotide polymorphisms of interleukin-6 in rheumatoid arthritis: A case-control study in Iraqi patients

BackgroundInterleukin-6 (IL-6) plays a significant role in pathogenesis of rheumatoid arthritis (RA), but its single nucleotide polymorphisms (SNPs), as well as therapy may modulate such role. ObjectivesIt was aimed to determine gene expression and six SNPs (rs1800796 C/G, rs7802307 A/C/T, rs7802308 A/T, rs36215814 A/G, rs184229712 A/G and rs867254801 C/G) of IL6 in etanercept-treated Iraqi Arab RA patients. Materials and methodsFifty-one RA patients and 45 controls were enrolled, and the determinations were carried out by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Sanger’s DNA sequencing. Disease activity and laboratory markers were considered in these evaluations, which were the first presentation in Iraqi patients. ResultsThe ΔCt mean of IL6 mRNA showed a significant increase in RA patients compared to control (9.084 ± 0.964 vs. 6.780 ± 2.240; p = 0.0001). In terms of a relative expression, the 2−ΔΔCt means showed no significant variations between subgroups of patients distributed by clinical and laboratory findings, with the exception of C-reactive protein (CRP). CRP-positive patients showed a lower mean compared to CRP-negative patients (0.201 ± 0.109 vs. 0.312 ± 0.131; p = 0.001). Distributing patients by gender and duration of disease also revealed significant variations between male and female patients. With respect to SNPs, allele and genotype frequencies of four SNPs (rs1800796, rs7802307, rs184229712 and rs867254801) showed variations between patients and controls, while no differences were reported for rs7802308 and rs36215814 SNPs. In addition, IL6 gene expression was significantly influenced by two SNP genotypes (rs36215814 GA and rs184229712 AG) compared to the corresponding GG genotypes. ConclusionGene expression of IL6 was down-regulated in RA patients, especially CRP-negative patients. Moreover, four SNPs of such cytokine may have a role in RA risk.

Association study on IL-4, IL-4Rα and IL-13 genetic polymorphisms in Swedish patients with colorectal cancer

BackgroundInterleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which share a common cellular receptor IL4Rα and are involved in the same signaling pathways. Our purpose was to assess whether genetic variants within IL-4, IL-13 and IL-4Rα are associated with the risk or clinical outcome of colorectal cancer (CRC). MethodsThree single nucleotide polymorphisms (SNPs) were screened in 466 patients with CRC and 445 healthy controls. The selected SNPs were IL-4 SNP rs2243250, IL-4Rα SNP rs1801275 and IL-13 SNP rs1800925. ResultsWe found that the genotype variant T/T in IL-13 gene was associated with a higher risk of CRC. Kaplan-Meier analysis showed that the cancer specific survival differed between C/C and CT + TT for IL-4 SNP. Moreover, the carriers of the T allele were associated with the highest risk of CRC death with a hazard ratio (HR) of 1.57, 95% CI 1.06–2.36, p = .024. The observed effect of the T allele was restricted to stage III patients. ConclusionOur results indicate IL-13 SNP rs1800925 as a risk factor for CRC and that IL-4 SNP rs2243250 could be a useful prognostic marker in the follow-up and clinical management of patients with CRC especially in stage III disease.

Validation of reported GLT6D1 (rs1537415), IL10 (rs6667202), and ANRIL (rs1333048) single nucleotide polymorphisms for aggressive periodontitis in a Brazilian population.

Aggressive periodontitis (AgP) is influenced by genetic factors. Recently, the single nucleotide polymorphisms (SNPs) rs1537415 (GLT6D1), rs6667202 (IL10), and rs1333048 (ANRIL) were associated with AgP in different European populations. However, these specific SNPs have not yet been determined in Brazilians. Therefore, this study investigated whether these SNPs previously associated with AgP could be replicated among Brazilians. The SNPs rs1537415, rs6667202, and rs1333048 were genotyped using 5'-nuclease allelic discrimination assay in AgP (n=200), chronic periodontitis (CP, n=190), and healthy patients (H, n=196). Differences in allele and genotype frequencies were analyzed using chi-square tests and stepwise logistic regression. The minor C allele of rs6667202 was less frequently detected in AgP patients (23.5%) when compared to non-AgP groups (H=34.2% and CP=30.3%; p<0.01), making the SNP protective against AgP occurrence. Moreover, the final logistic model for AgP diagnosis included gender (p=0.001) and the SNP rs6667202 (p<0.001) as significant variables. The SNPs rs1537415 and rs1333048 did not show associations with AgP. Only the SNP rs6667202 was associated with AgP in a Brazilian population, being the minor C allele protective against AgP. Moreover, SNPs rs1333048 and rs1537415, previously associated with AgP in other population, was not validated to Brazilian population.

Single nucleotide polymorphisms in cytokine/chemokine genes are associated with severe infection, ulcer grade and amputation in diabetic foot ulcer

Compared to other complications the genetics of diabetic foot ulcer is poorly studied. The Interleukin (IL)-6 (−174G > C/rs1800795), Tumor Necrosis Factor (TNF)-α (−308G > A/rs1800629) and (−238G > A/rs361525) and Stromal cell Derived Factor (SDF)-1 (+801G > A/rs1801157) are well characterized single nucleotide polymorphisms (SNPs) which were previously shown to be associated with Diabetic Foot Ulcer (DFU). In the present study, we looked at the association of these SNPs with foot microbial infection, Wagner's ulcer grade and treatment procedure, along with serum levels of these cytokines (intermediate phenotype) and other serum biomarkers (adiponectin, leptin, CRP and HOMA-IR) in subjects with DFU. Subjects with DFU (n = 270) were genotyped by PCR-RFLP and the serum levels of IL-6, TNF-α and SDF-1 were determined by ELISA. Microbial infections were determined by standard microbiological methods. Ulcer grade and treatment procedures were recorded. IL-6 (−174G > C), TNF-α (−308G > A) and SDF-1 (+801G > A) SNPs were associated with severe microbial infections. TNF-α (−308G > A) and (−238G > A) SNPs were associated with severe ulcer grades. SDF-1 (+801G > A) SNP was associated with major amputation even after adjusting for confounding variables. Identification of these SNPs in DFU subjects would help in identifying high risk individuals who need better treatment care.

Role of TNF −308 G/A, TNFβ +252 A/G and IL10 −592 C/A and −1082 G/A SNPs in pathogenesis of Immune Thrombocytopenia Purpura in population of Gujarat, India

Immune Thrombocytopenic Purpura (ITP) is an autoimmune disease, also known as Idiopathic Thrombocytopenia Purpura is characterized by the presence of antibodies against self-platelets. The etiology of ITP remains unclear, but it is generally accepted that both environmental and genetic factors and probably also a synergistic relationship between these factors, play important roles in the development of the disease. The etiological data for Indian population is insufficient. Several reports have suggested an association of cytokine polymorphisms with ITP, especially in occurrence and progression of acute ITP to chronic ITP disease. We therefore investigated association of candidate gene viz. TNFA (−308G/A), TNFB (+252A/G) and IL10 (−592C/A; −1082G/A) polymorphisms with Immune Thrombocytopenia Purpura in Population from Gujarat state of India.To investigate this, total 154 subjects (103 control and 51 ITP patients) were selected irrespective of sex. DNA was extracted and PCR-RFLP analysis was performed to assess the association of the above mentioned SNPs in patients 51 with respect to 103 controls.Results revealed that SNP of TNFA (−308) GA genotype was significantly higher in ITP patients (p < 0.0001, OR 7.8887 and 95% CI = 3.857–16.13) as well as elevated frequencies of recessive genotype AA (p < 0.001, OR = 11.40, 95% CI = 5.176–25.11) were present. Similarly, IL10 (−1082G/A) showed significant association with ITP patients with increased GA genotype frequency (p = 0.398, OR = 2.057, 95% CI = 1.030–4.109). The homozygous recessive genotype AA was also found to be significantly high (p < 0.0013, OR = 3.088, 95% CI = 1.541–6.190). However, we did not observe any association between TNFB(+252A/G) and IL10 (−592C/A) SNPs with ITP patients.Overall, our study suggests that the GA/AA genotype of the TNFA −308G/A and IL-10 −1082 polymorphism may be a significant genetic risk factor for the pathogenesis of ITP. Moreover, TNFA and IL-10 single nucleotide polymorphisms (SNPs) are known to be associated with altered expression of these proteins which may lead to dysregulation in downstream pathways of inflammation, thereby further strengthening the possibility, of role of inflammatory pathway's components in the development of ITP.

GWAS-identified CCR1 and IL10 loci contribute to M1 macrophage-predominant inflammation in Beh\xe7et\u2019s disease

BackgroundLow C-C chemokine receptor 1 (CCR1) and interleukin (IL)-10 expression is associated with risk of Behçet’s disease (BD). The objective of the present study was to clarify the pathological roles of CCR1 and IL10 loci identified by previous BD genome-wide association studies (GWASs).MethodsM1 and M2 macrophages (Mφ) were differentiated with granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor (M-CSF) from peripheral monocytes of healthy control subjects (HC) and patients with BD. Expression of CD68 and CD163 was evaluated to test for Mφ polarization. CCR1 and IL-10 messenger RNA (mRNA) and protein expression was compared according to CCR1 and IL10 single-nucleotide polymorphism (SNP) genotypes. The migratory ability of M1 and M2 Mφ toward CCR1 ligand macrophage inflammatory protein (MIP)-1α was compared. The ratio of M1 and M2 Mφ in skin lesions of BD and systemic sclerosis (SSc), which was reported to be M2 Mφ-dominant, was compared. To examine the plasticity of polarized Mφ, the differentiated cells were cultured with either the same or the other culture condition.ResultsPreferential expression of CD163, CCR1, and IL-10 was found in M2 Mφ compared with M1 Mφ. M2 Mφ migrated more sensitively to low concentrations of MIP-1α than M1 Mφ did. BD-derived M1 Mφ showed higher CCR1 surface expression than HC-derived M1 Mφ did. IL10 and CCR1 mRNA expression differences were observed by GWAS-identified SNP genotypes in polarized Mφ. BD skin lesions showed M1 Mφ predominance compared with SSc skin lesions. A plasticity assay revealed that M-CSF restored IL-10 synthesis and reduced IL-6 production by M1 Mφ.ConclusionsThe present study reveals that GWAS-identified SNPs contribute to M1 Mφ-predominant inflammation in BD. Our data also suggest that the skewed Mφ polarization is correctable by immunological intervention.

Association of Interleukin-6 Genetic Polymorphisms and Environment Factors Interactions with Coronary Artery Disease in a Chinese Han Population

ABSTRACTObjectives: To investigate the influence of IL-6 single nucleotide polymorphisms (SNPs), additional gene-gene and gene-environment interactions on coronary artery disease (CAD) risk. Methods: A total of 751 participants (429 CAD patients and 322 controls) were recruited in this study. Logistic regression analysis was conducted to evaluate the association of IL-6 SNPs with CAD risk and generalized multifactor dimensionality reduction (GMDR) was performed to investigate the best interaction combinations for gene-gene and gene-environment interactions. Results: CAD risk is significantly higher in carriers of C allele of the rs1800795 polymorphism than those with GG genotype (CC + CG versus GG, adjusted OR (95%CI) = 2.07 (1.56–2.86), p < 0.001). GMDR analysis revealed rs1800795 was significantly interacted with tobacco smoking and alcohol drinking in two-locus model (p < 0.0010). Current smokers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.22 (2.45–3.94) and current drinkers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.17 (2.20–4.24). Conclusion: The C allele of rs1800795 within IL-6 gene promoter, rs1800795-tobacco smoking and rs1800795-alcohol drinking interaction were all associated with increased CAD risk.

Polymorphisms in the promoter region of IL10 gene are associated with virus etiology of infant bronchiolitis.

Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (- 1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (- 3575A/T), rs1800871 (- 819C/T) or rs1800872 (- 592C/A) either alone or combined with the SNP at rs1800896 (- 1082G/A), and the etiology and severity of infant bronchiolitis. Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization. Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P = 0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than controls (65.5%, P = 0.009). Twenty-eight infants with bronchiolitis had the variant-variant Grs1800896Trs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures. IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and controls, but not between infants with respiratory syncytial virus bronchiolitis and controls.

Su1526 - Non Alcoholic Fatty Liver Disease and Metabolic Syndrome in Genotypes Non-3 Chronic Hepatitis C Infection: The Interplay of PNPLA3, IL-28 and IL-6 Single Nucleotide Polymorphisms

Su1526 - Non Alcoholic Fatty Liver Disease and Metabolic Syndrome in Genotypes Non-3 Chronic Hepatitis C Infection: The Interplay of PNPLA3, IL-28 and IL-6 Single Nucleotide Polymorphisms

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.

A pilot study of single nucleotide polymorphisms in the interleukin-6 receptor and their effects on pre- and post-transplant serum mediator level and outcome after allogeneic stem cell transplantation.

Interleukin (IL)-6 is an important regulator of immunity and inflammation in many diseases. Single nucleotide polymorphisms (SNPs) in the IL-6 gene influence outcome after allogeneic stem cell transplantation (ASCT), but the possible importance of SNPs in the IL-6 receptor has not been examined. We therefore investigated whether SNPs in the IL-6R gene influenced biochemical characteristics and clinical outcomes after ASCT. We examined the IL-6 promoter variant rs1800975 and the IL-6R SNPs rs4453032, rs2228145, rs4129267, rs4845374, rs4329505, rs4845617, rs12083537, rs4845618, rs6698040 and rs4379670 in a 101 population-based cohort of allotransplant recipients and their family donors. Patients being homozygous for the major alleles of the IL-6R SNPs rs2228145 and rs4845618 showed high pretransplant CRP serum levels together with decreased sIL-6R levels; the decreased IL-6R levels persisted 6 months post-transplant. In contrast, patients being homozygous for the minor allele of the IL-6R SNP rs4379670 showed decreased pretransplant CRP levels. Furthermore, the IL-6R rs4845618 donor genotype showed an association with severe acute graft-versus-host disease (GVHD), whereas the donor genotype of the IL-6 SNP rs1800795 was associated with decreased survival 100 days post-transplant. Finally, the recipient genotype of the IL-6R SNP rs4329505 showed a strong association with 2-years non-relapse mortality, and this effect was also highly significant in multivariate analysis. IL-6 and IL-6R SNPs influence the clinical outcome after allogeneic stem cell transplantation.

The IL20 Genetic Polymorphism Is Associated with Altered Clinical Outcome in Septic Shock

Background: The IL10 family of genes includes crucial immune regulators. We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock. Methods: Patients with septic shock (n = 1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981) were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day mortality. Results: Patients with the G allele of IL20 rs2981573 had a significantly increased hazard of death over the 28-day period compared to patients with the A allele in the septic shock cohort (adjusted hazard ratio 1.27; 95% confidence interval 1.10-1.47; p = 8.0 × 10^-4). Patients with the GG genotype had more organ dysfunction (p < 0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p < 0.05). The cardiac surgical ICU patients with the GG genotype had an increased length of ICU stay (p = 0.032). Conclusions: The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.

Associations of interleukin-10 gene polymorphisms with acute myeloid leukemia in human (Egypt).

Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous diseases, and characterization of transforming genetic events is becoming increasingly important. Interleukins (ILs) are a diverse set of small cell signaling protein molecules. Single nucleotide polymorphisms (SNPs) of ILs alter their function, increasing susceptibility to different diseases. We investigated the association between polymorphism in IL-10 -819T/C (rs1800871) and the risk of AML in the Egyptian population. DNA was isolated from bone marrow of 80 newly diagnosed adult AML patients, and 85 age- and sex-matched controls. Genetic analysis of IL-10 SNPs at -819T/C was assayed by polymerase chain reaction-restriction fragment length polymorphism. Genetic analysis of IL-10 revealed that the Egyptians have high -819T allele frequencies in apparently healthy controls, whereas -819CC genotype and the -819C allele frequencies in the AML group were higher than in the controls (P = 0.000086). The study suggested that subjects carrying the rs1800871CC genotype and C allele had a significantly increased risk for AML. IL-10 SNP at -819 was associated with enhanced AML risk, suggesting that rs1800871 provides clue for future studies and early detection of AML.

Association of TNF-α, IL-10 and IL-6 promoter polymorphisms in pulmonary tuberculosis patients and their household contacts of younger age group.

Single nucleotide polymorphisms (SNPs) of cytokine genes have been found to be involved in the clinical outcome of Tuberculosis. The present study was aimed to identify the high risk genotypes in Tuberculosis patients and their household contacts. A total of 490 subjects were studied which includes 150 active pulmonary tuberculosis patients (APTB), 190 household contacts (HHC) and 150 healthy controls (HC). The SNPs of TNF-α (-308A/G), IL-10(-1082G/A) and IL-6(-174G/C) were performed by ARMs PCR. The IL-10 GA genotype showed significant association in APTB and HHC and was 2.3 times higher risk in APTB and 3.7 times in HHC compared to HCs. The A allele was found to be significantly associated with the risk of disease. The CC genotype of IL-6 was found to be significantly associated in APTB and an insignificant positive association in HHCs. The multifactor dimensionality reduction (MDR) analysis indicated that the genotypes of IL-6 were showing high risk with GA genotype of IL-10. In conclusion the gene interaction may be useful for identification of genotypes as biomarkers to distinguish high risk individuals.

Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci

Eosinophilic esophagitis (EoE) is an esophageal inflammatory disease associated with atopic diseases. Thymic stromal lymphopoietin (TSLP) and calpain 14 (CAPN14) genetic variations contribute to EoE, but how this relates to atopy is unclear. The purpose of this study was to explore the relationship between EoE, atopy, and genetic risk. EoE-atopy enrichment was tested by using 700 patients with EoE and 801 community control subjects. Probing 372 single nucleotide polymorphisms (SNPs) in 63 atopy genes, we evaluated EoE associations using 412 nonatopic and 868 atopic disease control subjects. Interaction and stratified analyses of EoE-specific and atopy-related SNPs were performed. Atopic disease was enriched in patients with EoE (P<.0001). Comparing patients with EoE and nonatopic control subjects, EoE associated strongly with IL-4/kinesin family member 3A (IL4/KIF3A) (P=2.8×10-6; odds ratio [OR], 1.87), moderately with TSLP (P=1.5×10-4; OR, 1.43), and nominally with CAPN14 (P=.029; OR, 1.35). Comparing patients with EoE with atopic disease control subjects, EoE associated strongly with ST2 (P=3.5×10-6; OR, 1.77) and nominally with IL4/KIF3A (P=.019; OR, 1.25); TSLP's association persisted (P=4.7×10-5; OR, 1.37), and CAPN14's association strengthened (P=.0001; OR, 1.71). Notably, there was gene-gene interaction between TSLP and IL4 SNPs (P=.0074). Children with risk alleles for both genes were at higher risk for EoE (P=2.0×10-10; OR, 3.67). EoE genetic susceptibility is mediated by EoE-specific and general atopic disease loci, which can have synergistic effects. These results might aid in identifying potential therapeutics and predicting EoE susceptibility.