O polimorfismo VNTR no gene codificador do antagonista do receptor da interleucina-1 está associado com a doença arterial coronariana

Arman, Ahmet; Soylu, Özer; Yıldırım, Ahmet; Furman, Andrzej; Ercelen, Nesrin; Aydogan, Hakki; Coker, Ajda; Tezel, Tuna

doi:10.1590/s0066-782x2008001700002

Cited by 18 publications

(10 citation statements)

References 28 publications

(37 reference statements)

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“…A study in Polish population has reported an association of IL1B rs16944 with IA, but this could not be replicated in Italian population [ 16 , 17 ]. IL1RN VNTR polymorphism has been widely implicated in ischemic stroke [ 32 ] and coronary artery disease (CAD) [ 33 ]. In the present study, we failed to replicate these observations in IA patients from south India.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors

Sathyan

Koshy

Srinivas

et al. 2015

J Neuroinflammation

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BackgroundIntracranial aneurysm (IA) is often asymptomatic until the time of rupture resulting in subarachnoid hemorrhage (SAH).There is no precise biochemical or phenotype marker for diagnosis of aneurysm. Environmental risk factors that associate with IA can result in modifying the effect of inherited genetic factors and thereby increase the susceptibility to SAH. In addition subsequent to aneurismal rupture, the nature and quantum of inflammatory response might be critical for repair. Therefore, genetic liability to inflammatory response caused by polymorphisms in cytokine genes might be the common denominator for gene and environment in the development of aneurysm and complications associated with rupture.MethodsFunctionally relevant polymorphisms in the pro- and anti-inflammatory cytokine genes IL-1 complex (IL1A, IL1B, and IL1RN), TNFA, IFNG, IL3, IL6, IL12B, IL1RN, TGFB1, IL4, and IL10] were screened in radiologically confirmed 220 IA patients and 250 controls from genetically stratified Malayalam-speaking Dravidian ethnic population of south India. Subgroup analyses with genetic and environmental variables were also carried out.ResultsPro-inflammatory cytokines TNFA rs361525, IFNG rs2069718, and anti-inflammatory cytokine IL10 rs1800871 and rs1800872 were found to be significantly associated with IA, independent of epidemiological factors. TGFB1 rs1800469 polymorphism was observed to be associated with IA through co-modifying factors such as hypertension and gender. Functional prediction of all the associated SNPs of TNFA, IL10, and TGFB1 indicates their potential role in transcriptional regulation. Meta-analysis further reiterates that IL1 gene cluster and IL6 were not associated with IA.ConclusionsThe study suggests that chronic exposure to inflammatory response mediated by genetic variants in pro-inflammatory cytokines TNFA and IFNG could be a primary event, while stochastic regulation of IL10 and TGFB1 response mediated by comorbid factors such as hypertension may augment the pathogenesis of IA through vascular matrix degradation. The implication and interaction of these genetic variants under a specific environmental background will help us identify the resultant phenotypic variation in the pathogenesis of intracranial aneurysm. Identifying genetic risk factors for inflammation might also help in understanding and addressing the posttraumatic complications following the aneurismal rupture.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0354-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors

Sathyan

Koshy

Srinivas

et al. 2015

J Neuroinflammation

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“…Including the present study, two studies[ 38 ] were included for -1903 C>T (total sample: 1,041 with 524 cases and 517 controls), 9 studies[ 25 – 27 , 31 , 32 , 34 – 36 ] for -3954 C>T (total sample: 3,975 with 2,018 cases and 1,957 controls) and 2 studies[ 26 ] for -5887 C>T (total sample: 1,405 with 664 cases and 741 controls). Their data was meta-analyzed employing all three genetic models using appropriate effects for analysis.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-1 Gene Cluster Polymorphisms and Their Association with Coronary Artery Disease: Separate Evidences from the Largest Case-Control Study amongst North Indians and an Updated Meta-Analysis

et al. 2016

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Several researchers have reported significant association of numerous single nucleotide polymorphisms (SNPs) residing in the interleukin-1 (IL-1) gene cluster with coronary artery disease (CAD). However, their association status amongst North Indian ancestry (NIA) have never been systematically assessed. Despite a published meta-analysis on this subject, their association status worldwide as well as amongst different major ancestral subgroups still remains unclear. We therefore decided to prospectively test the association of 11 IL-1 gene cluster SNPs with CAD, vide a case-control study amongst a cohort of NIA and attempted to validate our results with the help of an updated meta-analysis of all relevant published association studies. Included studies were segregated into ancestral subgroups and association statuses for each subgroup were determined. A total of 323 cases and 400 healthy, age and sex matched controls belonging to NIA were prospectively enrolled and subsequently genotyped for 11 selected IL-1 gene cluster SNPs. Although results for none of the evaluated IL-1 gene cluster SNPs reached the adjusted level of significance (p<0.0045), clear trends of association were seen for IL1B -511 C>T and IL1RN 86bp VNTR in several of the constructed genetic models (p range = 0.01–0.044 and 0.005–0.034 respectively). The presence of >1, ‘T’ (minor) allele of IL1B -511 C>T in a genotype seemed to provide protection against CAD (OR = 0.62, p = 0.044), while the presence of >1, ‘C’ (major) allele seemed to increase the risk of CAD (OR = 1.36, p = 0.041). The minor allele (allele 2) of IL1RN 86bp VNTR and its homozygous genotype (2/2 genotype) also seemed to carry an increased risk for CAD (OR = 1.62, p = 0.005 and OR = 2.25, p = 0.031 respectively). On the other hand, several haplotype combinations constructed out of IL1B and IL1RN gene variants clearly showed statistically significant associations with CAD (p<0.0045). Our meta-analysis was conducted for 8 previously assessed IL-1 SNPs. We included 53 different studies which involved a total sample of 26,210 (13,982 cases and 12,228 controls). Our pooled results concurred with the findings of our case-control study and was not able to deduce any statistically significant associations for any of the 8 studied SNPs (p>0.05). Subgroup analysis, however, yielded interesting results, where significant differences in association statuses were seen for IL1A +4845 G>T, IL1B -511 C>T, IL1RN 86bp VNTR and IL1RN +8006 T>C for select ancestral subgroups. The hints of associations deduced for subjects belonging to NIA in our case-control study for both IL1B -511 C>T and IL1RN 86bp VNTR were duly validated vide significant p values seen for NIA in all three genetic models (OR range = 0.62–0.76, p range = 0.01–0.04 and OR range = 1.51–2.25, p range = 0.004–0.04 respectively). On the other hand, Mixed Ancestry (MA) subgroup carrying IL1B -511 C>T, IL1RN 86bp VNTR or IL1RN +8006 T>C polymorphisms seemed to enjoy significant protection against CAD. A few other ancestral subgroups also ...

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“…Furthermore, more than one study were included in each of the two papers by Francis et al [11] and Rios et al [26], respectively, and they were considered as separate studies in the following data analysis. Thus, thirteen studies [11], [14]–[17], [19]–[22], [26], [27] on IL-1B-511 polymorphism, nine studies [16], [19]–[24], [27], [29] on IL-1B+3954 polymorphism, twelve studies [11]–[14], [18]–[21], [25], [27], [28] on IL-1RN VNTR polymorphism were included in the final meta-analyses. A flow chart demonstrating the inclusion/exclusion of studies was displayed as Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Associations between Interleukin-1 Gene Polymorphisms and Coronary Heart Disease Risk: A Meta-Analysis

et al. 2012

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ObjectiveA great number of studies regarding the associations between IL-1B-511, IL-1B+3954 and IL-1RN VNTR polymorphisms within the IL-1gene cluster and coronary heart disease (CHD) have been published. However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations.MethodsPublished literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed- effect model.ResultsThirteen studies (3,219 cases/2,445 controls) for IL-1B-511 polymorphism, nine studies (1,828 cases/1,818 controls) for IL-1B+3954 polymorphism and twelve studies (2,987 cases/ 2,208 controls) for IL-1RN VNTR polymorphism were included in this meta analysis. The results indicated that both IL-1B-511 and IL-1B+3954 polymorphisms were not associated with CHD risk (IL-1B-511 T vs. C: OR = 0.98, 95%CI 0.87–1.09; IL-1B+3954 T vs. C: OR = 1.06, 95%CI 0.95–1.19). Similarly, there was no association between IL-1RN VNTR polymorphism and CHD risk (*2 vs. L: OR = 1.00, 95%CI 0.85–1.17).ConclusionsThis meta-analysis suggested that there were no associations between IL-1 gene cluster polymorphisms and CHD.

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O polimorfismo VNTR no gene codificador do antagonista do receptor da interleucina-1 está associado com a doença arterial coronariana

Cited by 18 publications

References 28 publications

Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors

Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors

Interleukin-1 Gene Cluster Polymorphisms and Their Association with Coronary Artery Disease: Separate Evidences from the Largest Case-Control Study amongst North Indians and an Updated Meta-Analysis

Associations between Interleukin-1 Gene Polymorphisms and Coronary Heart Disease Risk: A Meta-Analysis

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