Genetic Inflammatory Factors Predict Restenosis After Percutaneous Coronary Interventions

Abstract

Background-Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal factor in restenosis. Association studies have identified genes that may predispose to restenosis, but confirmation by large prospective studies is lacking. Our aim was to identify polymorphisms and haplotypes in genes involved in inflammatory pathways that predispose to restenosis. Methods and Results-The GENetic DEterminants of Restenosis (GENDER) project is a multicenter prospective study, including 3104 consecutive patients after successful PCI. Forty-eight polymorphisms in 34 genes in pathways possibly involved in the inflammatory process were analyzed. The 16Gly variant of the ␤ 2 -adrenergic receptor gave an increased risk of target vessel revascularization (TVR). The rare alleles of the CD14 gene (Ϫ260T/T), colony-stimulating factor 2 gene (117Thr/Thr), and eotaxin gene (Ϫ1328A/A) were associated with decreased risk of TVR. However, through the use of multiple testing corrections with permutation analysis, the probability of finding 4 significant markers by chance was 12%. Conclusions-Polymorphisms in 4 genes considered involved in the inflammatory reaction showed an association with TVR after PCI. Our results may contribute to the unraveling of the restenotic process. Given the explorative nature of this analysis, our results need to be replicated in other studies. (Circulation. 2005;112:2417-2425.)

Innate immunity has a dual effect on vascular healing: Suppression and aggravation of neointimal formation and remodeling post-endotoxin challenge

“…A recent study of the genetic inflammatory factors that predict restenosis after coronary interventions support the role of inflammation in modulating the vascular repair [22]. This corroborates the results of elevated inflammatory markers that are associated with worse outcome after PCI [23][24][25].…”

Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention

“…[3][4][5] Several inflammatory genes have already been reported to be associated with the development of restenosis. 6,7 However, little is known about the involvement of anti-inflammatory cytokines, although they seem logic candidate genes in the process of restenosis.…”

“…[8][9][10] Several of these factors have been demonstrated to be involved in the restenotic process. 5,11 The interindividual difference among individuals in their ability to produce IL-10 appears to have a genetic origin. [12][13][14] The heritability of the endotoxininduced IL-10 production has been estimated to be 74% in studies on monozygotic or dizygotic twins and nonrelated individuals.…”

The effect of interleukin-10 gene promoter polymorphisms on early-onset coronary artery disease

“…Furthermore, IL-10 plays a role in inhibition of cell adhesion molecules, monocyte chemotactic protein-1, tissue factor, fibrinogen, matrix metalloproteinase-9, T-lymphocyte granulocyte-macrophage colony-stimulation factor, inducible nitric oxide synthase and smooth muscle cell proliferation (7)(8)(9). Several of these functions of IL-10 are centered on inhibition of macrophage function, including cytotoxic activity and cytokine synthesis that was suggested as IL-10 may arrest and reverse the chronic inflammatory response in established atherosclerosis, as well as limit thrombotic complications (10,11).…”