Restenosis and Gene Polymorphisms

factors (local vessel wall trauma), humoral components and comorbidity like impaired glucose metabolism (diabetes mellitus). The role of diabetes mellitus as a risk factor for restenosis is complex, and may be either genetic predisposition, uncontrolled glucose level with increased molecular glycosylation or high insulin level (a growth factor) in type II diabetes mellitus. The recent development of high-density genotyping arrays provides opportunity for whole-genomic assessment of variants associated with common diseases [10] . Although more than 99% of human DNA sequences are the same across the population, variations in DNA sequence can have a major impact on how humans respond to environmental insults and even mechanical injury. In addition to the rapid progress in single nucleotide polymorphism (SNP) genotyping and the availability of appropriate large-scale epidemiological studies and clinical trials, an increasing number of studies of complex multigenic diseases, such as cancer, obesity, venous thrombosis, type 1 and type 2 diabetes as well as coronary artery disease have been published [11] . Interestingly, SNP are also evolutionarily stable – not changing much from generation to generation – making them easier to follow in population studies. Recent genome-wide studies have stated that human chromosome 9p21.3 harbors a locus with a common variant that significantly increases the risk of CAD and myocardial infarction (MI), making this the most highly replicated locus for CAD identified to Ever since the introduction of percutaneous transluminal coronary angioplasty and stenting for the treatment of patients with coronary artery disease (CAD), restenosis has been its Achilles heel, limiting long-term success. The use of stents resulted in larger final lumen cross-sectional area and abolished arterial remodeling to offset a stent-related increase in neointimal tissue accumulation as the result of smooth muscle cell proliferation [1, 2] . Drug-eluting stent (DES) with antiproliferative drugs attached via polymers on the stent surface have reduced restenosis and repeat revascularization rates by 50–90% compared with bare metal stent across all lesion and patient subsets [3–8] . With DES, there has been no change in the clinical and angiographic variables predicting restenosis, with similar molecular and histological manifestations [9] . However, major changes in molecular biology technology have occurred in the last decades, allowing us new insights into pathophysiological mechanisms and thus offering novel methods of diagnosis and potential therapy. Restenosis is a multifactorial biological process resulting from complex effects and interactions between extrinsic and intrinsic factors of predisposition. Intrinsic predisposition to restenosis may be genetic, including gender and racial influences. Multiple extrinsic factors may play a role in the development of restenosis, like anatomical vessel/lesion characteristics (small vessel size, long lesion, total occlusion, bifurcation lesions), technical Received and accepted: June 17, 2008 Published online: August 30, 2008