The role of three interleukin 10 gene polymorphisms (-?1082 A?>?G, -?819 C?>?T, -?592 A?>?C) in the risk of chronic and aggressive periodontitis: a meta-analysis and trial sequential analysis.
ABSTRACT: BACKGROUND:Periodontitis is a major oral health problem and it is considered as one of the reasons for tooth loss in developing and developed nations. The objective of the current review was to investigate the association between IL10 polymorphisms -?1082 A?>?G (rs1800896), -819C?>?T (rs1800871), -?592 A?>?C (rs1800872) and the risk of either chronic periodontitis or aggressive periodontitis. METHODS:This is a meta- analysis study, following the preferred reporting items for systematic reviews and meta- analyses (PRISMA). Relevant studies were searched in the health related electronic databases. Methodological quality of the included studies were assessed using the Newcastle-Ottawa Scale. For individual studies, odds ratio (OR) and its 95%confidence interval (CI) were calculated to assess the strength of association between IL10 polymorphisms (-?1082 A?>?G, -819C?>?T, -?592 A?>?C) and the risk of periodontitis. For pooling of the estimates across studies included, the summary OR and its 95% CIs were calculated with random-effects model. The pooled estimates were done under four genetic models such as the allelic contrast model, the recessive model, the dominant model and the additive model. Trial sequential analysis (TSA) was done for estimation of the required information size for this meta-analysis study. RESULTS:Sixteen studies were identified for this review. The included studies were assessed to be of moderate to good methodological quality. A significant association between polymorphism of IL10-1082 A?>?G polymorphism and the risk of chronic periodontitis in the non-Asian populations was observed only in the recessive model (OR,1.42; 95% CI:1.11, 1.8,I2: 43%). The significant associations between -?592 A?>?C polymorphism and the risk of aggressive periodontitis in the non-Asian populations were observed in particular genetic models such as allele contrast (OR, 4.34; 95%CI:1.87,10.07,I2: 65%) and recessive models (OR, 2.1; 95% CI:1.16, 3.82,I2: 0%). The TSA plot revealed that the required information size for evidence of effect was sufficient to draw a conclusion. CONCLUSIONS:This meta-analysis suggested that the IL10-1082 A?>?G polymorphism was associated with chronic periodontitis CP risk in non-Asians. Thus, in order to further establish the associations between IL10 (-?819 C?>?T, -?592 A?>?C) in Asian populations, future studies should include larger sample sizes with multi-ethnic groups.
Project description:Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single nucleotide polymorphisms (SNPs) in host immune related genes have been consistently suggested as participants in susceptibility towards disease. Interleukin-10 (IL-10) is a crucial immunomodulatory cytokine in mycobacterial pathogenesis and especially the -819C>T SNP (rs1800871) has been tested in several case-control studies indicating association with leprosy risk, although a recent consensus estimate is still missing. In this study, we evaluated the association of the -819C>T SNP and leprosy in two new Brazilian family-based populations. Then, we performed meta-analysis for this polymorphism summarizing published studies including these Brazilian family-based groups. Finally, we also retrieved published studies for other distal and proximal IL10 polymorphisms: -3575 T>A (rs1800890), -2849 G>A (rs6703630), -2763 C>A (rs6693899), -1082 G>A (rs1800896) and -592 C>A (rs1800872). Results from meta-analysis supported a significant susceptibility association for the -819T allele, with pooled Odds Ratio of 1.22 (CI = 1.11-1.34) and P-value = 3x10(-5) confirming previous data. This result remained unaltered after inclusion of the Brazilian family-based groups (OR = 1.2, CI = 1.10-1.31, P-value = 2x10(-5)). Also, meta-analysis confirmed association of -592 A allele and leprosy outcome (OR = 1.24, CI = 1.03-1.50, P-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r(2) = 1.0 between the -592C>A and -819C>T SNPs. We found no evidence of association for the other IL10 polymorphisms analyzed for leprosy outcome. Our results reinforce the role of the -819C>T as a tag SNP (rs1800871) and its association with leprosy susceptibility.
Project description:Background:Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has important roles in the periodontal diseases. The IL10-1082, -819, and -592 polymorphisms in the promoter region of IL-10 gene have been associated with various IL-10 expressions. The aim of this study was to investigate the association between these gene polymorphisms with chronic periodontitis in a sample of Iranian populations from Southeast of Iran. Materials and Methods:IL-10 single nucleotide polymorphisms were analyzed in 210 patients with chronic periodontitis (CP) and 100 individuals without CP by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis of data was performed using the Chi-square test. The risk associated with single alleles, genotypes, and haplotypes were calculated by performing a multiple logistic regression analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). P < 0.05 for statistical significance. Results:The prevalences of AG and GG genotypes of IL10-1082 were significantly different between CP and control groups in comparison to AA genotype (OR = 2.671; CI = 1.482-4.815; P = 0.001 for AG vs. AA, OR = 4.151; CI = 2.128-8.097; P < 0.001 for GG vs. AA). In addition, subjects with at least one IL10-1082-G allele were significantly had an increased risk for CP (OR = 2.157; CI = 1.531-3.038; P < 0.001). The distribution of the IL10-819 and IL10-592 genotypes was not different between CP and control subjects (P = 0.109 and P = 0.139, respectively). The combination of different genotypes showed that GCC haplotype was significantly different between groups (OR = 4.379; CI = 1.077-17.807; P = 0.039). Conclusion:The results demonstrated that IL10-1082 polymorphism was a putative risk factor for chronic periodontitis and associated with increased susceptibility to CP.
Project description:Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions -2849 , -1082 , -819 , and -592 and reconstructed the haplotypes. The IL10 low-producer haplotype -2849A/-1082A/-819C/-592C, compared to the high-producer haplotype -2849G/-1082G/-819C/-592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3-3.6) and PPD-positive controls (OR 2.09, CI 1.2-3.5). Lower IL-10 plasma levels in homozygous -2849A/-1082A/-819C/-592C carriers, compared to homozygous -2849G/-1082G/-819C/-592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy.
Project description:To assess the association between Interleukin-10 (IL-10) gene IL-10-1082 (G/A), IL-10-592(C/A), IL-10-819 (T/C) polymorphisms and hepatocellular carcinoma (HCC) susceptibility.Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for IL-10 polymorphisms and HCC were calculated in a ?xed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.This meta-analysis included seven eligible studies, which included 1012 HCC cases and 2308 controls. Overall, IL-10-1082 G/A polymorphism was not associated with the risk of HCC (AA vs AG + GG, OR = 1.11, 95% CI = 0.90-1.37). When stratifying for ethnicity, the results were similar (Asian, OR = 1.12, 95% CI = 0.87-1.44; non-Asian, OR = 1.10, 95% CI = 0.75-1.60). In the overall analysis, the IL-10 polymorphism at position -592 (C/A) was identi?ed as a genetic risk factor for HCC among Asians; patients carrying the IL-10-592*C allele had an increased risk of HCC (OR = 1.29, 95% CI = 1.12-1.49). No association was observed between the IL-10-819 T/C polymorphism and HCC susceptibility (TT vs TC + CC, OR = 1.02, 95% CI = 0.79-1.32).This meta-analysis suggests that IL-10-592 A/C polymorphism may be associated with HCC among Asians. IL-10-1082 G/A and IL-10-819 T/C polymorphisms were not detected to be related to the risk for HCC.
Project description:<h4>Objective</h4>Both variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.<h4>Methods</h4>We genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.<h4>Results</h4>The IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction ?=?0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] ?=?17.76 [6.17-51.06]) or the -592C (OR [95% CI] ?=?8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction ?=?0.080).<h4>Conclusions</h4>Inflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.
Project description:BACKGROUND:Interleukin-10 (IL-10) is a multifunctional regulatory cytokine that might be associated with increased risk of type 2 diabetes mellitus (T2DM). IL-10 gene polymorphisms have been reported to be associated with T2DM in several ethnic populations with controversial results. OBJECTIVES:This work is an updated meta-analysis aiming at the evaluation of the association between IL-10 gene polymorphisms: rs1800872 (- 592 C > A), rs1800896 (- 1082 A > G) and rs1800871 (- 819 C > T) with the risk of T2DM. METHODS:All available full text studies published up to July 2015 were included in this meta-analysis. Mainly Pubmed and Science Direct databases were searched for all eligible studies pertinent to testing the association between IL-10 gene polymorphisms with the susceptibility to T2DM. Further analyses of the pooled and stratified data in terms of individual polymorphic types and subject ethnicity were done and assessed using varied genetic models. RESULTS:Fifteen case-control studies with a total of 26 comparisons (10 for IL-10 - 592 C > A rs1800872, 11 for IL-10 - 1082 A > G rs1800896 and 5 for IL-10 - 819 C > T rs1800871 polymorphisms) met our inclusion criteria. IL-10 - 1082 A > G polymorphism was the only one to show an association with T2DM in all pooled sample particularly among Asian and European (high frequency of the G allele) ethnic groups. On the other hand, IL-10 - 592 C > A and - 819 C > T were significantly associated with T2DM only among African subjects. CONCLUSIONS:This meta-analysis demonstrated that IL-10 - 1082 A > G polymorphism was associated with increased risk of development of T2DM in total subjects no matter was their ethnic background, while both IL-10 - 592 C > A and - 819 C > T polymorphisms were associated with that risk only among African subjects.
Project description:Numerous studies have investigated the association of IL10 -819C>T and -592C>A polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility, and yet reported conflicting results. With this in mind, we performed the current meta-analysis with an aim to verify actual causative variants underlying lymphomagenesis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Moreover, to explore the biological function of these polymorphisms, we also performed genotype-based mRNA expression analysis using online database derived from 270 subjects within three ethnicities. The final analysis included 11 studies with a total of 5859 NHL cases and 6893 controls for the IL10 -819C>T polymorphism, and 11 studies with 6277 cases and 7350 controls for the IL10 -592C>A polymorphism. No significant association was observed for these two polymorphisms in either the overall analysis or the stratification analyses by ethnicity and source of controls. Nevertheless, stratification analyses demonstrated a significant decreased risk associated with the IL10 -819C>T polymorphism (homozygous: OR=0.81, 95% CI=0.66-0.99, and recessive model: OR=0.80, 95%CI=0.65-0.98) and IL10 -592C>A polymorphism (homozygous: OR=0.80, 95% CI=0.66-0.99, and recessive model: OR=0.80, 95%CI=0.66-0.97) among patients with diffuse large B-cell lymphoma (DLBCL). Despite some limitations, this meta-analysis indicates that polymorphisms in IL10 gene may contribute to DLBCL susceptibility.
Project description:OBJECTIVE:To evaluate the correlation between interleukin 10 (IL-10) -1082A/G polymorphism (rs1800896) and breast cancers by performing a meta-analysis. METHODS:The Embase and Medline databases were searched through 1 September 2018 to identify qualified articles. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were applied to evaluate associations. RESULTS:In total, 14 case-control studies, including 5320 cases and 5727 controls, were analyzed. We detected significant associations between the IL10 -1082 G/G genotype and risk of breast cancer (AA?+?AG vs. GG: OR?=?0.88, 95% CI?=?0.80-0.97). Subgroup analyses confirmed a significant association in Caucasian populations (OR?=?0.89, 95% CI?=?0.80-0.99), in population-based case-control studies (OR?=?0.87, 95% CI?=?0.78-0.96), and in studies with ?500 subjects (OR?=?0.88, 95% CI?=?0.79-0.99) under the recessive model (AA?+?AG vs. GG). No associations were found in Asian populations. CONCLUSIONS:The IL10 -1082A/G polymorphism is associated with an increased risk of breast cancer. The association between IL10 -1082 G/G genotype and increased risk of breast cancer is more significant in Caucasians, in population-based studies, and in larger studies.
Project description:BACKGROUND:Brucellosis is a quite normal zoonotic infection, which is caused by immediate contact with animals infected with Brucella or its products. IL-10 (-?1082?G/A, -?819 C/T, -?592C/A) and IL-6 -174?G/C polymorphisms have a great relationship with IL-10 and IL-6 production, which brings about Brucellosis pathogenesis and development. So far, the results of published literatures were controversial. Now, we perform a meta-analysis in different ethnic populations to get a more precise estimate of above polymorphisms with Brucellosis susceptibility. METHODS:Both OR and corresponding 95%CI were enrolled to make an assessment of the association strength through extracting genotyping frequency of cases and controls. The ?2-test based Q-statistic and I2 statistics were applied. If there was no evident heterogeneity, the fixed-effects model would be applied. If not, the random-effects model would be used. RESULTS:The significant associations were only found in Asian population of -?819 loci under three genetic models as follows: (Allele model: OR?=?0.60, 95%CI?=?0.44-0.82, P?=?0.001), (homozygote comparison: OR?=?0.24, 95%CI?=?0.09-0.62, P?=?0.003), (recessive genetic model: OR?=?0.22, 95%CI?=?0.05-0.91, P?=?0.036). CONCLUSION:In conclusion, IL-10?-?819 loci polymorphism contributes no risk to Caucasian population but may be associated with decreased risk in Asian population. And IL-10 -1082?G/A, 592 loci and IL-6 -174?G/C polymorphism are not associated with Brucellosis risk.
Project description:Interleukin-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.The 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.A 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.This 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.