Genetic predictive factors in restenosis

Abstract

Restenosis is still the main drawback of percutaneous transluminal coronary angioplasty (PTCA). It is thought to be a multifactorial process where recoil of the vessel, neointimal proliferation and thrombus formation are thought to play a role. Until now it has proven difficult to predict restenosis on clinical and procedural grounds, however, genetic epidemiology might provide more insights. In this review several genetic variables, i.e. polymorphisms that were determined in relation to restenosis are described. The single nucleotide polymorphisms (SNPs) described in the literature so far involve; the renin-angiotensin system, platelet aggregation, the inflammatory response, matrix metalloproteinases, smooth muscle cell proliferation, lipids and oxidative stress and nitric oxide. Nowadays DNA-microarrays have been developed which make it possible to test 50 or 60 polymorphisms at once. However, the risk of error due to multiple testing should be kept in mind. The results of the studies described should be interpreted with care. Many of the published studies are of relatively small sample size, which sometimes show more positive outcomes than the larger studies, this is possibly due to publication bias towards more positive results. The small sample size studies also exhibit wide confidence intervals. On the other hand, one must take into account that the process of restenosis is a multifactorial one and it is likely that multiple genes are involved. Thus, relatively small odds ratios relating to single gene contribution to restenosis can be of paramount importance when encompassed in the overall picture. Although still much research has to be done, stratification according to genetic make-up may enable tailoring of the interventional treatment to the individual patient.