Inflammatory Gene Haplotype-Interaction Networks Involved in Coronary Collateral Formation

Zhang, Jian; Regieli, Jakub J.; Schipper, Maria; Entius, Mark M.; Liang, Faming; Koerselman, Jeroen; Ruven, Henk J.T.; Graaf, Yolanda van der; Grobbee, Diederick E.; Doevendans, Pieter A.

doi:10.1159/000143407

Cited by 13 publications

(7 citation statements)

References 58 publications

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“…Different approaches have been undertaken to analyze the observed interaction effect [15], [16] between haplotypes or to investigate the presence of potential haplotypes interactions to partly explain the genetic variance in complex traits [17]. We tested our hypothesis under two different interaction models, a biological model that measures on an additive scale the risk difference between different exposures, and a statistical model on a multiplicative scale that considers the difference in the relative risk of a disease in the presence of both factors [18].…”

Section: Discussionmentioning

confidence: 99%

The Interaction between Coagulation Factor 2 Receptor and Interleukin 6 Haplotypes Increases the Risk of Myocardial Infarction in Men

Gigante

Bennet

Leander³

et al. 2010

PLoS ONE

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The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R) and the interleukin 6 (IL6) haplotypes modulates the risk of myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP). Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R) were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S), indicates the presence of a synergy (S>1) or of an antagonism (S<1). None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI) of 1.58 (1.05–2.41) (p = 0.02) in the crude and an OR of 1.72 (1.11–2.67) (p = 0.01) in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI) of 2.24 (1.27–3.95) (p = 0.005) and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI) of 1.56 (1.02–2.37) (p = 0.03) and S of 1.66 (0.89–31). In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.

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Section: Discussionmentioning

confidence: 99%

The Interaction between Coagulation Factor 2 Receptor and Interleukin 6 Haplotypes Increases the Risk of Myocardial Infarction in Men

Gigante

Bennet

Leander³

et al. 2010

PLoS ONE

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“…We and others have demonstrated the potential role of certain polymorphisms as factors associated with CCC [ 5 , 21 , 28 , 45 , 46 ], but usually they have not been validated in other cohorts of patients. In addition, SNPs may influence collateral development not only individually, but also when acting together with other SNPs, through gene haplotype networks, as demonstrated by the role of several inflammatory gene haplotype networks in CCC [ 65 ]. In conclusion, a validated SNP-based GWAS is needed to reveal and/or confirm the SNPs that predict coronary arteriogenic response.…”

Section: Discussionmentioning

confidence: 99%

Genetic association study of coronary collateral circulation in patients with coronary artery disease using 22 single nucleotide polymorphisms corresponding to 10 genes involved in postischemic neovascularization

Duran

Olavarría

Mola

et al. 2015

BMC Cardiovasc Disord

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BackgroundCollateral growth in patients with coronary artery disease (CAD) is highly heterogeneous. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors to coronary collateral circulation (CCC) is largely unknown. The goal of this study was to assess whether functional single nucleotide polymorphisms (SNPs) in genes involved in vascular growth are associated with CCC.Methods677 consecutive CAD patients were enrolled in the study and their CCC was assessed by the Rentrop method. 22 SNPs corresponding to 10 genes involved in postischemic neovascularization were genotyped and multivariate logistic regression models were adjusted using clinically relevant variables to estimate odds ratios and used to examine associations of allelic variants, genotypes and haplotypes with CCC.ResultsStatistical analysis showed that the HIF1A rs11549465 and rs2057482; VEGFA rs2010963, rs1570360, rs699947, rs3025039 and rs833061; KDR rs1870377, rs2305948 and rs2071559; CCL2 rs1024611, rs1024610, rs2857657 and rs2857654; NOS3 rs1799983; ICAM1 rs5498 and rs3093030; TGFB1 rs1800469; CD53 rs6679497; POSTN rs3829365 and rs1028728; and LGALS2 rs7291467 polymorphisms, as well as their haplotype combinations, were not associated with CCC (p < 0.05).ConclusionsWe could not validate in our cohort the association of the NOS3 rs1799983, HIF1A rs11549465, VEGFA rs2010963 and rs699947, and LGALS2 rs7291467 variants with CCC reported by other authors. A validated SNP-based genome-wide association study is required to identify polymorphisms influencing CCC.

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“…Inflammatory processes are activated during collateral vessel development [16][17][18] with inflammatory cells, including T cells, monocytes and natural killer cells in areas of collateral growth. 1 Mechanical stress can promote myocardial production of pro-inflammatory cytokines such as TNF-α and IL-6.…”

Section: Inflammatory Factors In the Midmyocardiummentioning

confidence: 99%

Repetitive ischemia increases myocardial dimethylarginine dimethylaminohydrolase 1 expression

et al. 2017

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Pharmacologic inhibition of nitric oxide production inhibits growth of coronary collateral vessels. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme that degrades asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase. Here we examined regulation of the ADMA-DDAH1 pathway in a canine model of recurrent myocardial ischemia during the time when coronary collateral growth is known to occur. Under basal conditions, DDAH1 expression was non-uniform across the left ventricular (LV) wall, with expression strongest in the subepicardium. In response to ischemia, DDAH1 expression was up-regulated in the midmyocardium of the ischemic zone, and this was associated with a significant reduction in myocardial interstitial fluid (MIF) ADMA. The decrease in MIF ADMA during ischemia was likely due to increased DDAH1 because myocardial protein arginine N-methyl transferase 1 (PRMT1) and the methylated arginine protein content (the source of ADMA) were unchanged or increased, respectively, at this time. The inflammatory mediators interleukin (IL-1β) and tumor necrosis factor (TNF-α) were also elevated in the midmyocardium where DDAH1 expression was increased. Both of these factors significantly up-regulated DDAH1 expression in cultured human coronary artery endothelial cells. Taken together, these results suggest that inflammatory factors expressed in response to myocardial ischemia contributed to up-regulation of DDAH1, which was responsible for the decrease in MIF ADMA.

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Inflammatory Gene Haplotype-Interaction Networks Involved in Coronary Collateral Formation

Cited by 13 publications

References 58 publications

The Interaction between Coagulation Factor 2 Receptor and Interleukin 6 Haplotypes Increases the Risk of Myocardial Infarction in Men

The Interaction between Coagulation Factor 2 Receptor and Interleukin 6 Haplotypes Increases the Risk of Myocardial Infarction in Men

Genetic association study of coronary collateral circulation in patients with coronary artery disease using 22 single nucleotide polymorphisms corresponding to 10 genes involved in postischemic neovascularization

Repetitive ischemia increases myocardial dimethylarginine dimethylaminohydrolase 1 expression

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