Inflammatory Gene Haplotype-Interaction Networks Involved in Coronary Collateral Formation

Article English OPEN
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. (2008)

Objectives: Formation of collateral circulation is an endogenous\ud response to atherosclerosis, and is a natural escape\ud mechanism by re-routing blood. Inflammatory responserelated\ud genes underlie the formation of coronary collaterals.\ud We explored the genetic basis of collateral formation in man\ud postulating interaction networks between functional Single\ud Nucleotide Polymorphisms (SNPs) in these inflammatory\ud gene candidates. Methods: The contribution of 41 genes as\ud well as the interactions among them was examined in a cohort\ud of 226 coronary artery disease patients, genotyped for\ud 54 candidate SNPs. Patients were classified to the extent of\ud collateral circulation. Stepwise logistic regression analysis\ud and a haplotype entropy procedure were applied to search\ud for haplotype interactions among all 54 polymorphisms.\ud Multiple testing was addressed by using the false discovery\ud rate (FDR) method. Results: The population comprised 84\ud patients with and 142 without visible collaterals. Among the\ud 41 genes, 16 pairs of SNPs were implicated in the development\ud of collaterals with the FDR of 0.19. Nine SNPs were\ud found to potentially have main effects on collateral formation.\ud Two sets of coupling haplotypes that predispose to collateral\ud formation were suggested. Conclusions: These findings\ud suggest that collateral formation may arise from the\ud interactions between several SNPs in inflammatory response\ud related genes, which may represent targets in future studies\ud of collateral formation. This may enhance developing strategies\ud for risk stratification and therapeutic stimulation of arteriogenesis.
  • References (31)
    31 references, page 1 of 4

    1 Hansen JF: Coronary collateral circulation: clinical significance and influence on survival in patients with coronary artery occlusion. Am Heart J 1989;117:290-295.

    2 Koerselman J, Van der Graaf Y, de Jaegere PP, Grobbee DE: Coronary collaterals: An important and underexposed aspect of coronary artery disease. Circulation 2003;107: 2507-2511.

    3 Seiler C: The human coronary collateral circulation. Heart 2003;89:1352-1357.

    4 Khaja F, Sabbah HG, Brymer JF, Stein PD: Influence of coronary collaterals on left ventricular function in patients undergoing coronary angioplasty. Am Heart J 1988;1174- 1180.

    5 Rogers WJ, Hood WP Jr, Mantle JA, Baxley WA, Kirklin JK, Zorn GL, Nath HP: Return of left ventricular function after reperfusion in patients with myocardial infarction: importance of subtotal stenoses or intact collaterals. Circulation 1984;338-349.

    6 Charney R, Cohen M: The role of the coronary collateral circulation in limiting myocardial ischemia and infarct size. Am Heart J 1993;937-945.

    7 Habib GB, Heibig J, Forman SA, Brown BG, Roberts R, Terrin ML, Bolli R: Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators. Circulation 1991;83:739-746.

    8 Rentrop KP, Cohen M, Blanke H, Phillips RA: Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985;5:587- 592.

    9 Wustmann K, Zbinden S, Windecker S, Meier B, Seiler C: Is there functional collateral flow during vascular occlusion in angiographically normal coronary arteries? Circulation 2003;107:2213-2220.

    10 Simons M: Angiogenesis: Where do we stand now? Circulation 2005;111:1556-1566.

  • Metrics
    0
    views in OpenAIRE
    0
    views in local repository
    11
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Kent Academic Repository - IRUS-UK 0 11
Share - Bookmark