The Interleukin-6-572G/C Gene Polymorphism and the Risk of Intracranial Aneurysms in a Chinese Population

Liu, Yi; Sun, Jianxin; Wu, Cong; Cao, Xudong; He, Min; You, Chao

doi:10.1089/gtmb.2012.0004

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…21 The evidence base was, however, small compared with other complex disorders. 21 The interleukin (IL)-6-572GG genotype has been shown to be associated with a heightened risk of IA in a Chinese population, 26 and this finding is consistent with other published reports in Chinese Han and Cantonese populations. 27,28 A region between introns 7 and 15 of the cyclindependent kinase inhibitor 2B antisense RNA-1 (CDKN2BAS) gene, carrying the rs1333040-T allele, has also been associated with an increased risk of IA in Japanese patients.…”

Section: Discussionsupporting

confidence: 87%

Angiotensin-converting enzyme insertion/deletion gene polymorphism and risk of intracranial aneurysm in a Chinese population

Liu

et al. 2013

J Int Med Res

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The relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphisms and intracranial aneurysm (IA) has been studied in Caucasian and Japanese populations. The present study aimed to investigate this association in a Chinese population. Methods: Patients with confirmed IA and age-and sex-matched control subjects without evidence of IA were enrolled. ACE I/D gene polymorphisms were analysed using polymerase chain reactionrestriction fragment length polymorphism. Results: A total of 220 patients with IA and 220 matched controls were enrolled. In the IA group, 64, 106 and 50 patients were of the II, ID and DD genotypes, respectively, compared with 44, 99 and 77 subjects in the control group. The ACE DD genotype and D allele frequencies were significantly lower in the IA group compared with the control group. There were no statistically significant differences in the site, shape, size and Fisher Grade of aneurysms between genotypes in patients with IA. Conclusion: The ACE DD genotype may be a protective factor for IA in a Chinese population.

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Section: Discussionsupporting

confidence: 87%

Angiotensin-converting enzyme insertion/deletion gene polymorphism and risk of intracranial aneurysm in a Chinese population

Liu

et al. 2013

J Int Med Res

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“…Morgan et al (2006) first reported that IL6 promoter polymorphism rs1800796 (−572C/G) and rs1800795 (−174G/C) are associated with IA in Caucasian population and 572C/174C haplotype having a greater risk [ 10 ]. Subsequent studies with these variants in Italian and Chinese population had shown conflicting results [ 11 – 14 ]. While rs1800796 and rs1800795 were not associated with IA in Italian population [ 11 ], it was a conflict of allelic associations in Chinese population.…”

Section: Discussionmentioning

confidence: 99%

“…While rs1800796 and rs1800795 were not associated with IA in Italian population [ 11 ], it was a conflict of allelic associations in Chinese population. In Han Chinese [ 12 ] and west Chinese population [ 14 ], G allele proved to be a risk allele, whereas in Cantonese population, C allele turned out to be a risk allele for IA [ 13 ]. None of these allelic associations for IL6 could be replicated in our study population for IA.…”

Section: Discussionmentioning

confidence: 99%

“…All the previous studies which explored similar variants in genes involved in inflammatory and anti-inflammatory cytokines were included in this study. The meta-analysis included the most studied SNPs in immune response, rs1800796 of IL6 [ 10 – 14 ], rs3212227 of IL12B [ 15 ], and rs16944 of IL1B [ 16 , 17 ] (Additional file 1 : Table S2). The inconsistency index I 2 was used to assess between-study heterogeneity.…”

Section: Methodsmentioning

confidence: 99%

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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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“…In these studies, 3 articles investigated the associations between TNF-α rs1800629 polymorphism and risk of IA; 13,14,17 11 articles investigated the associations between IL gene (IL-1α, IL-1β, IL6, and IL-12B) polymorphisms and risk of IA. 11,12,[17][18][19][20][21][22][23][24][25] Detailed characteristics of the included studies are summarized in Table 2. A detailed flow chart of study selection is presented in Fig.…”

Section: Characteristics Of the Available Studiesmentioning

confidence: 99%

Polymorphisms of Inflammatory Cytokine Genes and Risk for Intracranial Aneurysm: A Systematic Review and Meta-Analysis

Liao

et al. 2020

Yonsei Med J

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Purpose: Inflammatory cytokines are thought to be involved in the pathogenesis of intracranial aneurysm (IA), although results among studies in the literature are inconsistent. This article sought to review studies on the associations among polymorphisms in inflammatory cytokine genes and IA risk and to provide recommendations for future research. Materials and Methods: A systematic search of PubMed, Embase, and Web of Science was conducted up to August 4, 2019. The associations between polymorphisms of inflammatory cytokine genes and IA risk were estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed according to race. Qualitative systematic review was conducted for variants that were studied in only one study. All analyses were performed using STATA 12.0. Results: 13 studies investigating the associations between polymorphisms in five inflammatory cytokine genes (TNF-α, IL-1α, IL-1β, IL6, and IL-12B) and IA were reviewed. Combined results showed that the A allele of TNF-α rs1800629 polymorphism has a protective effect against IA (dominant model: OR=0.65, 95% CI=0.47-0.89, p=0.007). No associations were identified between polymorphisms in IL-1α rs1800587, IL-1β rs16944, IL6 rs1800795 and rs1800796, or IL-12B rs3212227 and IA risk. Conclusion: This review demonstrated an association between TNF-α rs1800629 polymorphism and IA in Caucasians, illustrating the potentially important role of genes involved in inflammation in IA.

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The Interleukin-6-572G/C Gene Polymorphism and the Risk of Intracranial Aneurysms in a Chinese Population

Cited by 14 publications

References 29 publications

Angiotensin-converting enzyme insertion/deletion gene polymorphism and risk of intracranial aneurysm in a Chinese population

Angiotensin-converting enzyme insertion/deletion gene polymorphism and risk of intracranial aneurysm in a Chinese population

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

Polymorphisms of Inflammatory Cytokine Genes and Risk for Intracranial Aneurysm: A Systematic Review and Meta-Analysis

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