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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, Hendrik J.T., van der Graaf, Yolanda, Grobbee, Diederick E, Doevendans, Pieter A. and others. (2008) Inflammatory Gene Haplotype-Interaction Networks Involved in Coronary Collateral Formation. Human Heredity, 66 (4). pp. 252-264. ISSN 0001-5652. (doi:10.1159/000143407)


Objectives: Formation of collateral circulation is an endogenous response to atherosclerosis, and is a natural escape mechanism by re-routing blood. Inflammatory responserelated genes underlie the formation of coronary collaterals. We explored the genetic basis of collateral formation in man postulating interaction networks between functional Single Nucleotide Polymorphisms (SNPs) in these inflammatory gene candidates. Methods: The contribution of 41 genes as well as the interactions among them was examined in a cohort of 226 coronary artery disease patients, genotyped for 54 candidate SNPs. Patients were classified to the extent of collateral circulation. Stepwise logistic regression analysis and a haplotype entropy procedure were applied to search for haplotype interactions among all 54 polymorphisms. Multiple testing was addressed by using the false discovery rate (FDR) method. Results: The population comprised 84 patients with and 142 without visible collaterals. Among the 41 genes, 16 pairs of SNPs were implicated in the development of collaterals with the FDR of 0.19. Nine SNPs were found to potentially have main effects on collateral formation. Two sets of coupling haplotypes that predispose to collateral formation were suggested. Conclusions: These findings suggest that collateral formation may arise from the interactions between several SNPs in inflammatory response related genes, which may represent targets in future studies of collateral formation. This may enhance developing strategies for risk stratification and therapeutic stimulation of arteriogenesis.

Item Type: Article
DOI/Identification number: 10.1159/000143407
Subjects: Q Science > QA Mathematics (inc Computing science) > QA276 Mathematical statistics
Divisions: Faculties > Sciences > School of Mathematics Statistics and Actuarial Science > Statistics
Depositing User: Jian Zhang
Date Deposited: 11 Oct 2012 17:32 UTC
Last Modified: 29 May 2019 09:34 UTC
Resource URI: (The current URI for this page, for reference purposes)
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