IL-10 Gene Promoter Polymorphisms Research Articles

A Common SNP of IL-10 (-1082A/G) is Associated With Increased Risk of Premenopausal Breast Cancer in South Indian Women.

Background:Evading the immune destruction and angiogenesis has been the two hallmarks of cancer. Interleukin-10 (IL-10) is a cytokine with immune suppressing (pro-tumorigenic) and anti-angiogenic (anti-tumorigenic) properties, thus making the role of IL-10 in tumorigenesis enigmatic. Previous studies have suggested a critical role of IL10 altered expression in complex process of tumor-microenvironment, co-evolution and tumorigenesis.Objectives:Evaluating the role of IL10 (-1082A/G) gene promoter polymorphism in breast cancer patients from South India.Patients and Methods:A case-control study was conducted with a total of 285 individuals, these include 125 histologically confirmed breast cancer patients and 160 age and sex matched controls. Genotypes were determined by allele-specific polymerase chain reaction (AS-PCR), followed by agarose gel electrophoresis. Statistical analysis was done to test the significance of results obtained.Results:Statistical analysis revealed that AA genotype of the Il-10 -1082A/G polymorphism is significantly associated with breast cancer (AA vs. AG: χ2 = 14.46, P = 0.0001432, OR = 2.854, 95% CI = 1.68 - 4.849). Up on stratifying subjects based on cancer stage, age at onset, menopausal status, AA genotype has associated with all the sub groups, except for post-menopausal women. There was no significant association which was observed with respected to hormonal status (ER, PR) and Her2/neu status.Conclusions:The present study suggests that IL-10 AA genotype as a risk factor in the etiology of breast cancer in the South Indian population.

Association of Interleukin-10 gene promoter polymorphisms with obstructive sleep apnea.

Interleukin-10 (IL) is an anti-inflammatory cytokine that regulates normal sleep patterns, and recent studies have reported that it is a potential useful biomarker to identify presence and severity of sleep apnea syndrome (OSAS). Promoter polymorphisms of IL-10 gene have been associated with altered expression levels, which contributes to OSAS. The aim of this study was to determine the prevalence of -1082 G/A, -819 C/T, and -592 C/A promoter polymorphisms of IL-10 gene in individuals with OSAS and controls. An open-label study was performed in the Otorhinolaryngology and Sleep Disorders Outpatient Clinics. One hundred four cases with OSAS were included as the study group, and 78 individuals without OSAS were included as the controls. DNAs were extracted from peripheral blood leukocytes, and the sites that encompassed those polymorphisms were identified by DNA sequencing analyses. Data were analyzed with SNPStats and multifactor dimensionality reduction (MDR) software. The prevalence of OSAS was higher in males in the study group when compared to controls (P = 0.0003). The IL-10-1082 G/A, -819 C/T, and -592 C/A SNPs, and their minor alleles were associated with a significantly increased risk for OSAS compared to the controls (P ˂ 0.05 for all). Furthermore, ATA haplotype frequency was significantly higher in the study group compared to the control group, but the GCC haplotype frequency was lower (P = 0.0001 and P = 0.0001). As indicated in MDR analysis, combinations of IL-10 gene were associated with OSAS in single-, double-, and triple-locus analyses. The prevalences of the IL-10 gene promoter polymorphisms were different in OSAS patients and the controls in Turkish population. IL-10 gene polymorphisms may lead to altered inflammatory cascade, which might contribute to OSAS. Further studies on larger cohorts are needed to validate our findings.

Cytokine gene polymorphisms in obstructive sleep apnoea/hypopnoea syndrome

ObjectiveThe pro-inflammatory cytokines, TNF-α, IL-6, and IL-8 are elevated in obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Cytokine gene interactions are complex and haplotype analysis may be more informative. We hypothesized that the effects of TNF-α in OSAHS might be due to linkage disequilibrium of the TNF-α (−308A) single nucleotide polymorphism (SNP) with other polymorphisms within the TNF-α gene, and that predisposition to elevated IL-6 and IL-8 levels in OSAHS might be attributable to pro-inflammatory IL-6 and IL-8 gene promoter polymorphisms. Method173 subjects were classified as having definite OSAHS or not on the basis of apnoea–hypopnoea frequency, sex, age, and symptoms. Population controls comprised 192 random UK blood donors. Genotyping was undertaken for the TNF- α promoter polymorphisms (−1031, −863, −857, −238), two lymphotoxin-α polymorphisms (intron 1 and Thr60Asn), the pro-inflammatory IL-6 gene promoter polymorphism (−174), and IL-8 gene promoter polymorphisms (−251; −781). ResultsThere was no significant difference between groups re: genotype/allelic frequency in the genes investigated. Association between disease status and the TNF-α alleles independently (TNF-103, TNF-803, TNF-857, TNF-238) with five haplotypes of TNF-α was not significant (p > 0.05). There was no difference in allelic or genotypic frequencies between obese and non-obese subjects with OSAHS. The TNF- α (−863A) allele alone, was significantly associated with obesity (OR 2.4; CI95% 1.1–5; p = 0.025). ConclusionOnly the TNF- α (308A) SNP appears to be significantly associated with OSAHS. The impact of cytokine gene polymorphisms on phenotypic expression of inflammation in OSAHS is likely to be complex.

IL-18 gene polymorphism in patients with visceral leishmaniasis in East Azarbaijan, Iran.

Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania species. According to the important role of cellular immunity against VL, this study was directed to determine the frequency of-607A/C and-137G/C genotypes on promoter region of interleukin-18 gene. The study groups included 91 patients with confirmed history of VL, 106 healthy seronegative, and 79 healthy seropositive individuals. All three groups were analyzed by amplification refractory mutation system polymerase chain reaction (ARMS-PCR). The highest rate of -607/A, and -607/C alleles was observed in seronegative individuals (66/67%) and in the patients (72/83%). Allele frequency of -607/C is more than -607/A allele in all groups. In position of-137, frequency of-137/G allele in all groups was more than -137/C. Statistical analysis of distribution of genotypes, did not reveal any significant difference among groups. On the basis of the results, there was no significant association between VL and polymorphism of IL-18 promoter. The results of this study showed that IL-18 gene promoter polymorphisms at positions-607 and-137 are not associated with VL in East Azerbaijan, Iran.

Interleukin-18 gene promoter polymorphisms and celiac disease in Italian patients.

Celiac disease (CD) is the most common food-sensitive enteropathy in genetically susceptible individuals. The major genetic risk factors known are specific human leukocyte antigen (HLA)-DQ haplotypes, but other genetic factors are supposed to be involved. Interleukin-18 (IL-18) is a pro-inflammatory cytokine that has an important role in the immune defense and it has the potential to influence inflammatory disorders. IL-18 is able to promote Th1 cell development and it is expressed in the mucosa of the small intestine in celiac patients. Given the IL-18 biological role, and since a few studies have previously suggested its involvement in CD, in order to investigate the role of IL18 gene in the susceptibility to CD we have performed a case-control study, analyzing two IL18 gene promoter polymorphisms, previously reported to impair the transcriptional activity of the gene, (-137G > C and -607C > A, rs187238 and rs1946518 respectively). A total of 556 CD Italian patients and 582 controls, further stratified for HLA class II (DQ) CD risk haplotypes were enrolled. The -607A > C A allele and A/A genotype, as well as the combination of this allele with the -137G allele in the AG haplotype, were associated with an increased risk towards CD development, in particular in HLA-DQ2.2 patients. Although the association was very moderate, our results indicate the possible involvement of IL18 gene in the susceptibility to CD, and for this reason we do think it should deserve further investigation.

Association study of IL-10 gene promoter polymorphisms and efficacy of risperidone treatment of schizophrenic patients with first episode

Objective To investigate association of IL-10 gene promoter polymorphisms with first episode schizophrenic and efficacy of risperidone. Methods 513 schizophrenic patients with first episode(patient group) and 627 health controls(control group)participated in this study. Genotyping for IL-10 gene label single nucleotide polymorphism(SNP)sites-592A/C (rs1800872), -1082A/G(rs1800896), -819T/C(rs1800871) were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)genotyping technology.513 patients were administered orally risperidone for 8 weeks.Clinical efficacy were evaluated with PANSS. Results The frequences of rs1800896 genotypes (332: 166: 15, 453: 161: 13; χ2=7.55, df=2, P=0.02) and alleles(830: 196, 1067: 187; χ2 =7.09, df=1, P=0.008, OR=1.35, 95%CI=1.08~1.68) showed significant differences between patient group and control group, however only allele differences showed statistical significance after Bonferroni correction(P=0.024). The frequencies of rs1800872and rs1800871 genotypes and alleles had no significant differences between patient group and control group(P>0.05). There were no significant differences of haplotype frequences between patient group and control group(P>0.05). There were no significant differences of genotypes (134: 209: 38, 61: 59: 12; χ2=5.16, df=2, P=0.08; 244: 129: 8, 88: 37: 7; χ2=4.57, df=2, P=0.10; 188: 158: 35, 54: 64: 14; χ2 =2.80, df=2, P=0.25)and alleles (477: 285, 181: 83; χ2=3.03, df=1, P=0.08; 617: 145, 213: 51; χ2 =0.01, df=1, P=0.92; 534: 228, 172: 92; χ2=2.22, df=1, P=0.14) frequences of rs1800872, rs1800896, rs1800871 between effective group(381cases) and invalid group(132 cases) of Risperidone efficacy(P>0.05), while ATC haplotype frequences had significant difference between two groups(χ2=7.501, P=0.006, OR(95%CI)=2.420(1.262-4.640)). Conclusion IL-10 gene rs1800896 polymorphism may be associated with susceptibility to schizophrenia.The clinical curative effect of risperidone in the treatment of schizophrenia is associated with ATC haplotype, ATC haplotype may be good predictors to the overall curative effect of risperidone. Key words: First episode schizophrenia; Gene polymorphisms; Interleukin 10; Risperidone tablets

FLT3 expression and IL10 promoter polymorphism in acute myeloid leukemia with RUNX1-RUNX1T1.

We investigated the correlation between FLT3 expression and IL10 gene promoter polymorphism in acute myeloid leukemia with RUNX1-RUNX1T1 and their clinical significance. FLT3 mRNA expression was measured by real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) on bone marrow (BM) leukemic cells. IL10 gene promoter polymorphisms including rs1800896 (G-1082A), rs1800871 (C-819T), and rs1800872 (C-592T) were genotyped by direct sequencing. Among 45 enrolled patients, 32 (71.1 %) exhibited FLT3 overexpression, whose FLT3 mRNA level was higher than normal cut-off value (0.02). The IHC results also consisted with FLT3 mRNA expression data achieved by qPCR. The FLT3 mRNA level was significantly different among 3 IHC staining groups (P < 0.0001); 0.031 ± 0.041, 0.106 ± 0.097 and 0.588 ± 0.573 in IHC negative, intermediate and positive group, respectively. Interestingly, the FLT3 expression level was correlated with the percentage of BM CD34 positive cells (R = 0.360, P = 0.016). The elevated FLT3 expression at initial BM were decreased after remission and maintained lower than the cut-off level. FLT3 expression was not dependent on IL10 gene promoter polymorphisms. FLT3 overexpression itself did not demonstrate significant effects on overall survival (OS). However, it is notable that IL10 rs1800896 GA genotype tended to have a lower estimated mean OS (20.1 months) compared to GG genotype (54.6 months), but the statistical significance was not derived because of limited number of patients in this study (P = 0.072). Further studies including more type of leukemia and patients may be helpful to understand the relations between cytokine genotype and FLT3 expression and their prognostic impact.

ANALYSIS OF CORRELATION BETWEEN IL 6 GENE POLYMORPHISM (-174 G /C) AND CLASSIC RISK FACTORS IN PATIENTS WITH PREVIOUS MYOCARDIAL INFARCTIONS

We have carried out a prevalence analysis of IL6 (-174 G/C) gene promoter polymorphism and traditional cardiovascular risk factors in male patients living in the West Siberia that survived myocardial infarction (MI) in their anamnesis. Analysis of genotype frequencies have shown decrease of *-174 GG genotype in the patients with MI. Frequency of the same genotype is decreased among smoking patients as compared to healthy non-smokers. On other hand, an increased body weight and arterial pressure indexes increase is found in IL6*-174 G patients, versus healthy population. Hence, the analyzed IL6 (-174 G/C) polymorphism may be considered as an additional predisposition factor for development of vascular damage.

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients.

Interleukin (IL)-18 is a well-known major proinflammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited. This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples. In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients. The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients.

IL-6 gene promoter polymorphisms: genetic susceptibility to recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is defined as three or more pregnancy losses before 20 weeks. RPL is a multifactorial condition with several etiologic factors including genetic abnormalities of the parents, anatomical, endocrinological, hematologic and immunologic abnormalities, infections, nutritional and environmental factors. The causes of pregnancy loss in about half of the women with RPL even after extensive investigations remain unknown. We analyzed IL-6 -174 G/C, -572 G/C, -597 G/A, -1363 G/T, -2954 G/C promoter region polymorphisms in 113 RPL patients and 113 healthy subjects by using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay. The -174G/C genotypic and -174C allelic frequency and the -2954G/C genotypic and -2954C allelic frequency of IL-6 was higher in RPL patients than healthy controls and a significant association was found between RPL and -174G/C, -2954G/C polymorphisms (p < 0.0001, OR: 0.28, 95% CI: 0.15-0.51, p < 0.034, OR: 0.16, 95% CI: 0.01-1.12 respectively). We found remarkably similar frequencies in RPL patients compared to controls for IL-6 -572G/C,-597G/A and -1363G/T genotypes/alleles and no association was observed between RPL and these polymorphisms. Our study supported that IL-6 -174G/C and -2954G/C polymorphisms were associated with an increased risk of RPL in Turkish patients (Tab. 3, Ref. 24).

IL-6 gene promoter polymorphisms and risk of coronary artery disease in a Chinese population.

We investigated the relationships between single nucleotide polymorphisms (SNPs) of the interleukin (IL)-6 gene 174 G>C (rs1800795), 572 G>C (rs1800796), and 597 G/A (rs1800797) and coronary artery disease (CAD) risk in a Chinese population. This case-control study recruited 296 CAD patients and 327 controls between January 2009 and May 2012. Genotyping of IL-6 174 G>C (rs1800795), 572 G>C (rs1800796), and 597 G/A (rs1800797) was performed on a 384-well plate format using the Sequenom MassARRAY platform. CAD patients were more likely to be older and male, with a higher body mass index, diabetes, and hypertension, and presented higher triglycerides, and lower total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. We found that the IL-6 174CC genotype was associated with a significantly increased risk of CAD compared to the wild-type GG genotype in a codominant model [odds ratio (95% confidence interval) = 1.94 (1.13-3.37)], whereas IL-6 174 G>C polymorphisms presented an increased risk of CAD in dominant and recessive models. However, we did not find that the IL-6 572 CC and 597 AA genotypes were correlated with an increased risk of CAD. IL-6 174 G>C rs1800795 was associated with CAD risk in a Chinese population. Further large-scale studies are required to determine whether IL-6 SNPs interact with environmental factors in the development of CAD.

The role of single nucleotide polymorphism of IL-6 and IL-10 cytokine on pain severity and pain relief after radiotherapy in multiple myeloma patients with painful bone destructions

Multiple myeloma (MM) cells interact with bone marrow stromal cells stimulating transcription and secretion of cytokines like IL-6 and IL-10, which are implicated in the progression and dissemination of MM. Regulation of cytokines secretion is under genetic control through genetic polymorphisms in their coding and promoter sequences. It seems that single nucleotide polymorphism (SNP) in the promoter region of various genes may regulate the plasma concentrations of cytokines. Cytokines could be also hypothesized to function as pain modulators as peripheral nociceptors are sensitized by cytokines. The aim was to determine if the SNP of IL-6 and IL-10 cytokines could influence the analgesic response of radiotherapy in the treatment of painful bone destructions in MM patients. 30 patients (19 women and 11 men, median age: 67 years) with MM and painful bone destructions were treated with palliative radiotherapy. Pain was evaluated according to the visual analogue scale and analgesics intake. Pain scores and analgesics use were measured prior to radiotherapy as well as 4, 12 and 24 weeks afterward. Opioid analgesics were converted to the morphine-equivalent daily dose (MEDD). Genomic DNA was extracted from peripheral blood leukocytes and IL-6 and IL-10 gene promoter polymorphisms were analysed with polymerase chain reaction. 60% of patients reported severe pain prior to radiotherapy, which decreased to 13% at the first follow-up visit (p &lt;0.001). The MEDD on admission to the hospital was 75 mg/day which decreased to 46 mg/day at the first follow-up visit (p = 0.033). A significant parameter in pain relief was: age &lt; 65 years (p=0.029). We analysed 6 SNPs in the gene promoter region of IL-6 (-597 G/A, -572 G/C, -174 G/C) and IL-10 (-592 A/C, -819 C/T, -1082 A/G) as well as their relation with pain severity and analgesic consumption. Patients who are IL-10 -1082 A/G carriers are prone to respond better to radiotherapy than other patients (p&lt;0.05). A borderline association was noted for patients who are IL-6 -597 A/A and G/G carriers - assumed to be at higher risk for severe pain prior to radiotherapy (p=0.07) while for patients who are IL-10 - 1082 A/A carries: the median pain score decreased faster (p=0.08). Patients with genotypes IL-6 -597 A/A and IL-6 -174 C/C required a smaller dose of opioids (p=0.06). SNP of IL-6 and IL-10 cytokines can influence the analgesic response of radiotherapy. Patients with genotype IL-10 -1082 A/G respond better to radiotherapy.

Interleukin-10 (−1082G/A) gene promotor polymorphism in Egyptian non-Hodgkin lymphoma patients: relation to other prognostic factors

Background and Objectives Interleukin-10 (IL-10) is an important immunoregulatory cytokine in. It is part of a balanced network of cytokines and can be cancer promoting (immunosuppressive; stimulation of cell proliferation) or cancer inhibiting. The present study aimed at investigating possible association between IL10 (-1082G/A) gene promoter polymorphism in a sample of Egyptian Non-Hodgkin lymphoma patients and its relation to other prognostic factors. Design and Methods A case control study was carried out on fifty NHL patients at first diagnosis and twenty age and sex- matched normal controls. Results There was statistically insignificant correlation between IL10 (-1082G/A) genotype and age (P = 0.631), ESR (P = 0.087), serum LDH (P = 0.623), serum albumin (P = 0.108) serum β2 microglobulin (P = 0.578), and hemoglobin (P = 0.696) in patient group. The frequency of IL10-1082G allele was found to be higher in patients with NHL(28.3%) as compared with control subjects (12.5%)(P = 0.298) , with a higher frequency of IL-10-1082GG/GA genotypes in the former population (13.1%, 30.4%) versus (5.0%, 15.0%) χ2P = 0.073. Conclusion The frequency of IL10-1082G allele was found to be higher in patients with NHL as compared with healthy controls, which is translated into a higher frequency of IL-10-1082GG/GA genotypes, thus may be associated with higher risk of developing NHL. There was no significant correlation between IL-10 polymorphism with other prognostic factors.

Interleukin 10 gene promoter polymorphism and risk of diffuse large B cell lymphoma (DLBCL)

PurposeGiven the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin’s lymphoma (NHL), this work was designed to study the impact of IL-10 (−1082 G/A; rs1800896 and −819 C/T; rs1800871) gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma (DLBCL); the major type of NHL. To the best of our knowledge, this study is the first one that examines IL-10 promoter polymorphism in DLBCL in Egyptians. MethodsGenotyping polymorphism is performed using sequence-specific primers polymerase chain reaction (SSP-PCR) in 100 Egyptian DLBCL patients and 119 normal controls. Circulating plasma levels of IL-10 were measured using Enzyme-linked immunosorbent assay (ELISA). ResultsInsignificant change in IL-10 (−1082 and −819) genotypes was recorded. Although A allele is slightly decreased in DLBCL patients, it did not reach statistical significance. GT haplotype was significantly elevated (P<0.05) in NHL patients. A significant linkage disequilibrium between the −1082 and −819 SNPs with D′=0.596 and r2=0.1032 (P<0.001) was demonstrated. Significantly increased plasma IL-10 (P<0.01) was found which is positively correlated (r=0.307; P<0.01) with the disease. ConclusionsTaken together, our findings demonstrated that IL-10 promoter gene polymorphism (−1082 and −819) may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine gene polymorphisms will lead to a better understanding of the disease’s biological background.

Association of Interleukin-18 Gene Promoter −607 C&gt;A and −137G&gt;C Polymorphisms with Cancer Risk: A Meta-Analysis of 26 Studies

BackgroundEvidence suggest that IL-18 gene polymorphisms may be risk factors for several cancers. Increasing studies investigating the association between IL-18 gene promoter polymorphisms (−607 C>A and −137G>C) and cancer risk have yielded conflicting results.Methodology/Principal FindingsWe performed a meta-analysis of 26 studies including 4096 cases and 5222 controls. We assessed the strength of the association of IL-18 gene promoter −607 C>A and −137G>C polymorphisms with cancer risk and performed sub-group analyses by cancer types, ethnicities, source of controls and sample size. The pooled results revealed a significant increased risk of cancer susceptibility for −607 C>A (CA vs. CC: OR = 1.19, 95%CI: 1.04, 1.37, Pheterogeneity = 0.033; CA/AA vs. CC: OR = 1.17, 95% CI: 1.01, 1.34, Pheterogeneity = 0.007), but no significant association for −137 G>C was observed with overall cancer risk. Sub-group analyses revealed that an increased risk of nasopharyngeal carcinoma was both found for −607 C>A (CA/AA vs. CC: OR = 1.32, 95% CI: 1.04, 1.69, Pheterogeneity = 0.823) and −137G>C (GC/CC vs. GG: OR = 1.57, 95%CI: 1.26, 1.96, Pheterogeneity = 0.373). Consistent with the results of the genotyping analyses, the −607A/−137C and −607C/−137C haplotypes were associated with a significantly increased risk of nasopharyngeal carcinoma as compared with the −607C/−137G haplotype (−607A/−137C vs. −607C/−137G: OR = 1.26, 95%CI: 1.13, 1.40; Pheterogeneity = 0.569; −607C/−137C vs. −607C/−137G: OR = 1.14, 95%CI: 1.03, 1.27; Pheterogeneity = 0.775). As for gastrointestinal cancer, we also found that −607 C>A polymorphism was significantly associated with increased cancer risk (CA/AA vs. CC: OR = 1.25, 95% CI: 1.05, 1.50, Pheterogeneity = 0.458). Further sub-group analysis revealed that −137G>C polymorphism contributed to cancer risk in Asians but not in Caucasians (GC/CC vs. GG: OR = 1.31, 95%CI: 1.05, 1.64, Pheterogeneity<0.001).ConclusionsThe meta-analysis results suggest that IL-18 gene promoter −607 C>A polymorphism is significantly associated with overall cancer risk, especially in nasopharyngeal carcinoma and gastrointestinal cancer; and the −137 G>C polymorphism is associated with increased overall cancer risk in Asian populations and also significantly increases the risk of nasopharyngeal carcinoma.

Interleukin-6 promoter polymorphisms −174 G/C in Brazilian patients with systemic lupus erythematosus

To investigate the association of the IL-6 gene promoter polymorphism (-174 G/C) with SLE susceptibility and disease features in Brazilian patients, a case-control study of 80 lupus cases and 60 volunteer healthy women was performed. Genotyping was carried out by polymerase chain reaction and PCR product was digested by HSP92II restriction enzyme, being after visualized in polyacrylamide gel. There were significant differences in the distribution of the IL-6 gene C/C polymorphism between the SLE and control groups (χ(2) = 8.668; P = 0.0032). Individual carriers of the variant allele G had a 1.98 (95% CI: 1.0844-3.6353)-fold increased risk for SLE. Besides, association was observed in frequency of C allele (P = 0.0247; OR = 0.5036) between SLE patients and control groups. This study presents preliminary evidence for association between IL-6 polymorphism and SLE susceptibility in a Northeast population from Brazil.

Association of Cytokine and Cytokine Receptor Gene Polymorphisms with the Risk of Chronic Hepatitis B

Hepatitis B (HBV) infection is a major cause of chronic liver diseases, and the polymorphisms of cytokine genes may affect the progression of HBV-related hepatitis. The aim of this study was to examine the association of cytokine polymorphisms with the susceptibility to HBV-related chronicity. Specifically, a LIFECODES Cytokine SNP Typing kit was used to investigate 22 cytokine single nucleotide polymorphisms (SNPs) from 14 cytokine and cytokine receptor genes with the aim of analyzing the role of Th1 and Th2 genotype combination. This population-based case-control association study included 131 chronic HBV patients and a control group of 142 healthy donors. When the combination of Th1 and Th2 genotypes was analyzed for the genetic risk factor for chronic hepatitis B, we did not observe any significant association. A non-significant association betweenTh1 and Th2 and this risk factor could have resulted from the limitation of our small sample size. When the results from each genotype were separately analyzed, the frequencies of the heterozygous CA (-592) and CT (-819) genotype of IL-10 gene-promoter polymorphisms were significantly higher in chronic HBV patients than that in healthy controls (OR=1.76, 9%CI =1.03-3.01, p =0.028; OR=1.79, 95%CI =1.04-3.06, p =0.024, respectively). Interestingly, the TCC (-1098/-590/-33) haplotype frequency of IL-4 showed a positive association with chronic hepatitis B as a protective haplotype (OR =0.53, 95%CI =0.32-0.85, p =0.005). These preliminary results suggest that polymorphisms in some cytokine genes, particularly the Th2 cytokine, influence persistence of HBV infection.

Association between interleukin-10 promoter polymorphisms and endometriosis: A meta-analysis

To investigate the influence of the interleukin-10 gene promoter polymorphisms on the susceptibility of endometriosis, we examined the association by performing a meta-analysis. The PubMed, Embase, HuGE Navigator and CNKI were searched to identify eligible studies. We then conducted a meta-analysis to examine the association between interleukin-10 gene promoter polymorphisms and endometriosis. Eight case–control studies which examined the association between the IL-10 gene promoter polymorphisms and the susceptibility to endometriosis were finally included in the meta-analysis. Meta-analysis of the IL-10 −592 A/C polymorphisms showed a significant increased risk of endometriosis in the overall and Asian population in all genetic models and allele contrast. However, meta-analysis of the IL-10 −1082 A/G and IL-10 −819 T/C polymorphisms showed no association with endometriosis in all genetic models and allele contrast in the overall and Asian population samples. In addition, there was not a significant association between the IL-10 −592 A/C gene promoter polymorphisms with the severity of endometriosis.In conclusion, this meta-analysis suggests that the IL-10 −592 A/C polymorphisms conferred susceptibility to endometriosis. However, no associations were found between the IL-10 −1082 A/G and −819 T/C polymorphisms and susceptibility to endometriosis. Further studies are required to elucidate these associations more clearly.

The Influence of Human Leukocyte Antigen and IL-10 Gene Polymorphisms on Hepatitis B Virus Outcome

The clinical outcome of hepatitis B virus (HBV) infection is variable, ranging from spontaneous recovery to an inactive carrier state, chronic hepatitis, occult HBV infection, liver cirrhosis, or hepatocellular carcinoma. This variable pattern and clinical outcomes of the infection were mainly determined by virological and host genetic factors. Since the most of host genetic factors associated with HBV infection have currently focused on human leukocyte antigen (HLA) associations and interleukin (IL)-10 gene polymorphisms, this review focuses on the recent progresses in these issues to provide prognostic markers for the outcome of HBV infection. A study on serum levels of IL-10 in occult HBV infected patients reported that the higher level of IL-10 production may suppress function of the immune system against HBV in patients with occult HBV infection. IL-10 promoter polymorphism at position -592 is associated with susceptibility to occult HBV infection. Findings of this study suggest that the host HLA polymorphism is an important factor in determining outcome of HBV infection but regarding IL-10 gene promoter polymorphisms, we are still have a long way to achieve a definite conclusion.

520 Involvement of Il-10 Gene Promoter Polymorphisms in the Susceptibility for Childhood Asthma

BackgroundAsthma and atopy have a complex background which may result from the interaction of genes and environments. Interleukin (IL)-10 is known to play various roles in immune-regulating and anti-inflammatory responses. The aim of this study was to evaluate the possible effect of the IL-10 promoter polymorphisms on susceptibility to childhood asthma.MethodsWe recruited 333 patients with atopic asthma, 55 with non-atopic asthma, and 248 normal controls. We performed a genetic association study of 3 genetic polymorphisms (IL-10–1082A>G, IL-10 –819T>C, –592A>C) of the IL-10 promoter.ResultsThere was no difference between atopic asthma, non-atopic asthma and normal controls in allele, genotype or haplotype frequencies of these IL-10 polymorphisms. However, the –1082A>G polymorphism and ATA haplotype in the IL-10 promoter gene were associated with airway hyperresponsiveness (AHR) and the –819T>C, –592A>C, and ATA and ACC haplotypes were also shown to be related with serum eosinophil cationic protein (ECP).ConclusionsOur results suggest that the polymorphisms within the IL-10 promoter may have a disease-modifying effect in asthmatic airway.