Interleukin-10 Gene Promoter Polymorphisms Research Articles

Association of interleukin-10 gene promoter polymorphism in spontaneous abortions: a family-based triad study.

The present study is a triad study designed to determine the co-relation of IL-10 -819C/T promoter polymorphism with the risk of spontaneous abortions. A total of 50 families with spontaneous abortions and 60 families with medically terminated pregnancies were considered for the present study. Fetal tissue of less than 20 weeks of gestation along with peripheral blood from all the couples was collected in this study. A standard amplification refractory mutation system-polymerase chain reaction was carried out to determine the IL 10 genotype in all the subjects. Odd's ratio and their respective 95% confidence intervals were used to determine the strength of association between IL-10 promoter gene polymorphism and spontaneous abortions. The study revealed a statistically significant association of IL-10 -819C/T polymorphism between the two family groups among fetuses (p=0.0000003) and mothers (p=0.0000001). No significant difference was observed in the genotype distribution of IL-10 among fathers. An increased frequency of TT genotype and T allele was observed in spontaneously aborted fetuses and their mothers compared to respective controls. In conclusion, IL-10 C -819T gene promoter polymorphism may act as a major genetic regulator in the etiology of spontaneous abortions.

Interleukin-18 gene polymorphisms and risk of recurrent pregnancy loss: A systematic review and meta-analysis.

Interleukin-18 (IL-18) plays a potential pathological role in recurrent pregnancy loss (RPL). The results of published studies on the relationship between IL-18 gene promoter polymorphisms (-137G/C and-607C/A) and RPL risk remain controversial. This meta-analysis was performed to evaluate the association of IL-18, -137G/C and-607C/A gene polymorphisms with the risk of RPL under recessive, dominant and additive genetic models. A literature search was conducted in Medline, Embase and Web of Science for studies that described the effect of IL-18 gene polymorphisms on RPL risk. The numbers of each -137G/C and-607C/A genotype in the case and control groups were extracted. Quality of the original studies' methodology was also assessed. Meta-analysis was performed using Stata 13.1 software and the fixed effect model was used. Five articles were included in this meta-analysis. No significant heterogeneity between the studies was noted. The IL-18 -137 G/C polymorphism was significantly associated with an increased risk of RPL under a recessive genetic model (CC vs. GG + CG: odds ratio = 1.56, 95% confidence interval = 1.13 ~ 2.15). For the -607C/A mutation, we failed to find any association under any genetic models. The Egger's regression asymmetry test showed no publication bias. Our present study indicates a positive association between the CC genotype of the IL-18 -137G/C gene and RPL risk. Future well-designed large studies are needed to validate the association between IL-18 gene polymorphisms and the risk of RPL.

Impact of the IL-10 Promoter Gene Polymorphisms in the Severity of Chronic Hepatitis B Infection

Background:Interleukin-10 (IL-10) is an important anti-inflammatory cytokine. The polymorphisms of its promoter gene have been considered to be related with the chronicity of hepatitis B infection.Objectives:The aim of this study was to evaluate the polymorphisms at different positions in the IL-10 promoter gene in patients with chronic hepatitis B.Patients and Methods:Totally, 166 patients with chronic hepatitis B infection were enrolled. Genotypes at different positions (i.e. -819, - 592, and - 1082) in the IL-10 gene promoter were determined.Results:The C/A genotype at position -592, C/T genotype at position -819, and GCC/ATA haplotype of the IL-10 gene promoter were significantly more common in the patients with cirrhosis. The genotypes were significantly different between the hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients at position -592 (C/A and C/C), position -819 (C/C and C/T), and position -1082 (A/A and G/A).Conclusions:Some IL-10 promoter gene polymorphisms predisposed the infected hepatitis B virus cases to cirrhosis in our study 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.

IL-10 gene promoter and intron polymorphisms as genetic biomarkers of cervical cancer susceptibility among Tunisians

ObjectiveWe investigated the association between polymorphisms in the promoter and intron regions of the interleukin-10 (IL-10) gene with the risk of cervical cancer (CC) in Tunisian patients and control women. MethodsStudy subjects comprised 86 CC cases and 126 control women. Genotyping of IL-10 intron (rs3024491, rs3024490) and promoter (rs1800872, rs1800871, rs1800896) variants was done by real-time PCR, with defined clusters. ResultsThe minor allele frequencies of the five tested IL-10 SNPs were not significantly different between cervical cancer cases and control women. However, significantly higher frequencies of homozygous minor allele-carriers in cases was seen for rs3024490 (P=0.023), rs1800872 (P=0.037), and rs1800871 (P=0.028). IL-10 serum levels were significantly reduced in rs3024490 T/T vs. G/G genotype carriers, and in rs1800871 T/T than C/C genotype carriers. While carriage of rs1800872 and rs3024491 minor allele was associated with reduced IL-10 secretion, this was not statistically significant. Haploview analysis demonstrated high linkage disequilibrium (LD) among the IL10 SNPs studied, and only seven haplotypes were common, capturing 98.8% of the total possible haplotypes. Reduced frequency of haplotypes GTCCA (P<0.001) and TGATG (P<0.001) was seen in cervical cancer cases than in control women, thus conferring disease protection nature to these haplotype. This association remained significant for GTCCA (Pc=0.006) and TGATG (P=0.045) after correcting for multiple comparisons. ConclusionSpecific IL-10 variants (rs3024490, rs1800872, and rs1800871) and haplotype (GTCCA and TGATG) may contribute to the development of cervical cancer among Tunisian women.

Lack of Association between Interleukin-10 Gene Polymorphisms and Graft Rejection Risk in Kidney Transplantation Recipients: A Meta-Analysis.

BackgroundInterleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations.MethodsThe PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity.ResultsA total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85–1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79–1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85–1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79–1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients.ConclusionThis meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed to confirm our results.

Interleukin-10 promoter gene polymorphisms and susceptibility to tuberculosis: a meta-analysis.

ObjectiveAs an update to other recent meta-analyses, the purpose of this study was to explore whether interleukin-10 (IL-10) polymorphisms and their haplotypes contribute to tuberculosis (TB) susceptibility.MethodsWe searched for published case-control studies examining IL-10 polymorphisms and TB in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang databases and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strengths of the associations.ResultsA total of 28 studies comprising 8,242 TB patients and 9,666 controls were included in the present study. There were no significant associations between the -1082G/A, -819C/T, and -592A/C polymorphisms and TB in the pooled samples. Subgroup analyses revealed that the -819T allele was associated with an increased TB risk in Asians in all genetic models (T vs. C: OR=1.17, 95% CI=1.05-1.29, P=0.003; TT vs. CC: OR=1.37, 95% CI=1.09-1.72, P=0.006; CT+TT vs. CC: OR=1.33, 95% CI=1.09-1.63, P=0.006; TT vs. CT+CC: OR=1.17, 95% CI=1.02-1.35, P=0.03) and that the -592A/C polymorphism was significantly associated with TB in Europeans under two genetic models (A vs. C: OR=0.77, 95% CI=0.60-0.98, P=0.03; AA vs. CC: OR=0.53, 95% CI=0.30-0.95, P=0.03). Furthermore, the GCC IL-10 promoter haplotype was associated with an increased risk of TB (GCC vs. others: P=1.42, 95% CI=1.02-1.97, P=0.04). Subgroup analyses based on ethnicity revealed that the GCC haplotype was associated with a higher risk of TB in Europeans, whereas the ACC haplotype was associated with a lower TB risk in both Asians and Europeans.ConclusionsThis meta-analysis suggests that the IL-10-819T/C polymorphism is associated with the risk of TB in Asians and that the IL-10-592A/C polymorphism may be a risk factor for TB in Europeans. Furthermore, these data indicate that IL-10 promoter haplotypes play a vital role in the susceptibility to or protection against the development of TB.

P039: Interleukin‐10 gene promoter polymorphisms and the outcome of Hepatitis B Virus infection

Journal of Viral HepatitisVolume 22, Issue S2 p. 38-39 Poster PresentationFree Access P039: Interleukin-10 gene promoter polymorphisms and the outcome of Hepatitis B Virus infection First published: 25 June 2015 https://doi.org/10.1111/jvh.37_12425AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume22, IssueS2Special Issue: 15th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) held from June 26th to 28th, 2015, in Berlin, GermanyJune 2015Pages 38-39 RelatedInformation

Interleukin-10 gene promoter polymorphism and risk of liver cirrhosis.

We conducted a hospital-based case-control study to assess the association between IL-10-592 A/C, IL-10-819 C/T, and IL-10-1082 A/G polymorphisms and the risk of liver cirrhosis in a Chinese population. This 1:1-matched case-control study included 192 patients from the Chinese PLA General Hospital. Genotypes of IL-10-592 A/C, IL-10-819 C/T, and IL-10-1082 A/G were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis. Conditional regression analysis showed that individuals carrying the IL-10-1082 G allele had an only slightly increased risk of liver cirrhosis, with an adjusted odds ratio (95% confidence interval) of 2.14 (0.97-1.68). However, we did not identify a significant association between polymorphisms in IL-10-592 A/C and IL-10-819 C/T and the risk of liver cirrhosis. These findings may provide important clues for future studies of early detection screening of liver cirrhosis.

Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset.

Evidence suggests that interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites -1082 (A/G) and -819 (C/T) in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction (cerebral infarction group) and 115 healthy subjects (control group). We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups (χ2 = 6.643, P = 0.010). The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group (92.3%) than in the control group (86.1%) (P = 0.015). Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype (OR = 2.031, 95%CI: 1.134–3.637). In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction (OR = 2.073, 95%CI: 1.278–3.364). No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups (P > 0.05). These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.

Interleukin-10 polymorphisms and nasopharyngeal carcinoma risk: a meta-analysis.

It has been reported that interleukin-10 (IL-10) promoter genes (1082 A/G, 819 T/C, 592 A/C) are associated with nasopharyngeal carcinoma (NPC). However, the results remain controversial and ambiguous. To resolve inconsistencies in published data, we performed a meta-analysis to ascertain the association between IL-10 polymorphisms and NPC risk. Two case-control studies and two cohort studies were quantitatively analyzed to evaluate IL-10 promoter gene polymorphisms and NPC risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for each genetic model and allelic comparison. A random-effect model or a fixed-effect model was used to calculate the overall combined risk estimates. Overall, the variant genotypes (AA and AG) of the IL-10-1082 A/G polymorphism were associated with elevated risk of NPC compared with the GG homozygote (AG vs GG: OR = 1.77; 95%CI = 1.39-2.26; AG + GG vs AA: OR = 1.78; 95%CI = 1.42-2.22); no significant associations were observed in allelic contrast and the recessive model. Strong positive association was seen in the cohort studies but not in the case-control studies. No statistically significant association was detected between IL-10-819 T/C and IL-10-592 A/C polymorphisms and NPC. Additionally, publication bias was not found. Based on the current evidence, this meta-analysis suggests that IL-1082 A/G polymorphism may increase the risk of NPC, but IL-10-819 T/C and IL-10-592 A/C polymorphisms do not. Further multicenter studies that are better controlled are required to confirm these findings.

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.

P35: Evaluation of interleukin‐10 gene promoter polymorphism ( 819 C/T) in patients with chronic hepatitis B virus infection

Journal of Viral HepatitisVolume 21, Issue s2 p. 41-41 Poster SessionFree Access P35: Evaluation of interleukin-10 gene promoter polymorphism ( 819 C/T) in patients with chronic hepatitis B virus infection First published: 08 October 2014 https://doi.org/10.1111/jvh.12333_34AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issues2Special Issue: Abstracts for the Viral Hepatitis Congress 2014, 9–11 October 2014, Frankfurt, GermanyOctober 2014Pages 41-41 RelatedInformation

Association of IL-18 promoter gene polymorphisms with rheumatoid arthritis: a meta-analysis.

Interleukin-18(IL-18) plays a potential pathological role in rheumatoid arthritis (RA). The conclusions of the published reports on the relationship between single-nucleotide polymorphisms -607C/A (rs1946518) and -137G/C (rs187238) located in the IL-18 gene promoter and RA risk remain controversial. This meta-analysis was performed to evaluate the association between IL-18 gene promoter (-607A/C and -137C/G) polymorphisms and RA using (1) allele, (2) codominant, (3) dominant, and (4) recessive models. Literature search was conducted up to January, 2013, in PubMed, EMBASE, Spring-link, Web of Science, Wanfang (Chinese) and China National Knowledge Infrastructure (CNKI). A total of 10 studies from eight articles involving 2,662 cases and 2,168 controls for -607A/C polymorphism and 9 studies from six articles involving 1,331 cases and 1,468 controls for -137C/G polymorphism were considered in the meta-analysis. For the relationship of IL-18 -607A/C polymorphism with RA risk, significant association was observed in allele model (OR = 0.778, 95 % CI = 0.633-0.955) and dominant model (OR = 0.618, 95 % CI = 0.466-0.819). However, no significant association could be observed between -137C/G polymorphism and RA risk under all genetic models (allele model: OR = 0.940, 95 % CI = 0.777-1.138; codominant model: OR = 1.079, 95 % CI = 0.574-2.029; dominant model: OR = 0.913, 95 % CI = 0.779-1.069; recessive model: OR = 1.133, 95 % CI = 0.586-2.190). In the subgroup analysis by ethnicity, significant result was also found in Asian populations but not found in Caucasian populations for the relationship of IL-18 -607A/C polymorphism with RA risk; while no obvious association was found between IL-18 -137C/G polymorphism and RA risk. This meta-analysis indicates that IL-18 -607A/C polymorphism in promoter region may be associated with RA risk.

Haplotype analysis of interleukin-10 gene promoter polymorphisms in chronic hepatitis C infection: a case control study.

High prevalence of hepatitis c virus (HCV) infection in some areas necessitates more investigations of the causative factors. Genetic factors that cause disruption in operation or secretion of interleukin 10 (IL-10), an anti-inflammatory cytokine, may play a role in the intensity of the disease. The aim of this study was to evaluate genetic variants of IL-10 gene polymorphisms in HCV patients and their relationship with HCV disease. Fifty HCV patients and the same number of healthy individuals who were referred to hepatitis clinic in Mashhad, northeast of Iran, were recruited. Genomic DNA was extracted from whole blood. Genotyping for IL-10 gene promoter polymorphisms in three positions (-1082 G>A, -819 C>T and -592 C>A) was conducted by amplification refractory mutation system-polymerase chain reaction. Haplotype analysis was performed using PHASE software. In a recessive analysis model of the -1082 position (GG vs. AA+AG), GG genotype was more common in patients (adjusted p = 0.02; OR = 4.66 [95% CI 1.31-16.35]). Also, ATA haplotype was more prevalent in HCV patients (adjusted p = 0.061; OR = 1.87 [95% CI 0.97-3.61]). Also, ATC/GCA diplotypes were more common in controls (adjusted p=0.002; adjusted OR = 0.27 [95% CI 0.11-0.63]). Although we found a possible association between IL-10 promoter polymorphisms and HCV infection, certain genotypes or diplotypes may confer a higher risk or susceptibility for developing HCV infection.

Association between interleukin-10 promoter gene polymorphisms and acute graft-versus-host disease after hematopoietic stem cell transplantation: A systematic review and meta-analysis

ObjectivesInterleukin-10 (IL-10) is an important immunomodulatory cytokine. The association between IL-10 promoter gene polymorphisms and acute graft-versus-host disease (aGVHD) risk is established; however, results of these studies remain inconclusive. We performed a meta-analysis to clarify the effects of IL-10 promoter gene polymorphisms on aGVHD risk.MethodsThe authors searched MEDLINE, EMBASE, and Cochrane Library databases. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity.ResultsFinally, a total of 11 studies encompassing 3588 recipients and 3221 donors were included to study IL-10 -1082 G > A, -819 C > T, and -592 C > A polymorphisms. IL-10 -819 CC genotype was associated with an increased aGVHD risk (grade I–IV: OR, 2.722 (95% CI, 1.360–5.450); grade II–IV: OR, 2.265 (95% CI, 1.015–5.053)). Furthermore, patients who received grafts from donors with an IL-10 -819 CC genotype experienced more frequent grade I–IV aGVHD (OR, 2.306 (95% CI, 1.168–4.551)). Recipients with IL-10 -592 CC genotypes were at increased risk for grade II–IV aGVHD (OR, 1.999 (95% CI, 1.230–3.250)). Together, this meta-analysis found that IL-10 -819 CC and -592 CC polymorphisms increased aGVHD risk.Discussion and ConclusionThis meta-analysis found the evidence that the IL-10 -819 CC and -592 CC genotypes in both recipients and donors increased the risk of aGVHD in allogeneic hematopoietic stem cell transplantation (HSCT) patients. These results contribute towards improving patient outcome through insight and rationale for individualized treatment strategies considering genetic determinants.

Interleukin-6 and interleukin-10 gene promoter polymorphisms and risk of endemic Burkitt lymphoma.

Overexpression of interleukin-6 (IL-6) and IL-10 in endemic Burkitt lymphoma (eBL) may facilitate tumorigenesis by providing a permissive cytokine milieu. Promoter polymorphisms influence interindividual differences in cytokine production. We hypothesized that children genetically predisposed for elevated cytokine levels may be more susceptible to eBL. Using case-control samples from western Kenya consisting of 117 eBL cases and 88 ethnically matched healthy controls, we tested for the association between eBL risk and IL-10 (rs1800896, rs1800871, and rs1800872) and IL-6 (rs1800795) promoter single nucleotide polymorphisms (SNPs) as well as IL-10 promoter haplotypes. In addition, the association between these variants and Epstein Barr Virus (EBV) load was examined. Results showed that selected IL-10 and IL-6 promoter SNPs and IL-10 promoter haplotypes were not associated with risk eBL or EBV levels in EBV-seropositive children. Findings from this study reveal that common variants within the IL-10 and IL-6 promoters do not independently increase eBL risk in this vulnerable population.

IL-6, IL-10 and IL-17 gene polymorphisms in Iranian women with recurrent miscarriage.

Pro-inflammatory and anti-inflammatory cytokines and polymorphisms of their genes have been described to be involved in the pathogenesis of recurrent miscarriage (RM). To investigate the association between RM and five polymorphisms of cytokine genes, interleukin 10 (IL-10), (-592 A/C, -819 C/T, -1082 A/G), IL-6 (-174 C/G) and IL-17 (-197 G/A) in Iranian women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to determine the frequencies of the IL-6, IL-10 and IL-17 gene polymorphisms in 85 women with RM compared with 104 healthy controls. The frequencies of IL-10 promoter gene polymorphisms (-592 A/C and -819 C/T) were significantly higher in RM women than those in controls (p=0.003). However, no statistically significant differences were observed in the frequencies of IL-6 (-174 C/G), IL-10 (-1082 A/G) and IL-17 (-197 G/A) polymorphisms between RM women and controls. These results suggest that IL-10 gene polymorphism screening might have some relevance in patients with RM, a suggestion which requires further studies.

Interleukin-10 gene promoter polymorphisms in celiac patients from north-eastern Italy

Celiac disease is a complex chronic intestinal disorder driven by an immune response against the gliadin fraction of gluten: many factors are involved in the pathogenesis of the disease, and among these Interleukin-10 could play an important role. In the present study, the −1082A>G, −819T>C and −592A>C IL10 functional polymorphisms were analyzed in 565 celiac patients and 576 healthy controls from north-eastern Italy, stratified for HLA class II celiac disease risk haplotypes. No significant differences were observed for the three IL10 polymorphisms distribution between celiac patients and controls with the exception of a slightly increased risk for the −1082A allele in HLA-DQ8 male individuals. Although our findings suggest that the IL10 genetic variants analyzed do not have a major role in the susceptibility to the development of celiac disease in north-eastern Italian patients, we think that the possible involvement of IL10 gene in CD should deserve further investigation and that large-scale studies are recommended to confirm our findings.

Absence of association of interleukin-18 gene polymorphisms with primary immune thrombocytopenia in a Chinese Han population.

Interleukin-18 (IL-18) is an inflammatory cytokine that plays an important role in autoimmune disease by inducing interferon-γ secretion. Considering the abnormal serum concentration of IL-18 in primary immune thrombocytopenia (ITP) patients and the regulated effect of IL-18 gene polymorphisms on its production, the aim of this study was to investigate a possible association between the IL-18 promoter polymorphisms (-137 G/C and -607 C/A sites) and genetic susceptibility to ITP in a Chinese Han population. A total of 181 ITP patients and 163 healthy controls were included in this study; IL-18 gene promoter polymorphisms were analyzed by a polymerase chain reaction with sequence-specific primers. No significant differences in genotype (-607: χ(2)=0.307, p=0.858; -137: χ(2)=0.378, p=0.828) and allele frequencies (-607: χ(2)=0.004, p=0.949; -137: χ(2)=0.307, p=0.858) were found between total ITP patients and normal controls. We further analyzed the association of IL-18 polymorphisms with clinical parameters of ITP patients, including first onset age and clinical therapy response to glucocorticoids, and no difference was revealed. In conclusion, IL-18 promoter polymorphisms may not be associated with genetic susceptibility to ITP in a Chinese Han population.