Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease

• Published in: The hematology journal : the official journal of the European Haematology Association Vol. 2; no. 3; pp. 197 - 201
• Main Authors: ZEE, R. Y. L, HOH, J, MACAYA, C, PINTOR, E, FERNANDEZ-CRUZ, A, OTT, J, LINDPAINTNER, K, CHENG, S, REYNOLDS, R, GROW, M. A, SILBERGLEIT, A, WALKER, K, STEINER, L, ZANGENBERG, G, FERNANDEZ-ORTIZ, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 2002; Nature Publishing Group
• Subjects: Angioplasty; Angioplasty, Balloon, Coronary; Apolipoproteins; Arteries; Balloon treatment; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular Diseases - epidemiology; CD14 antigen; Cell Cycle - genetics; Cohort Studies; Complications and side effects; Constriction, Pathologic - epidemiology; Constriction, Pathologic - genetics; Coronary artery; Coronary heart disease; Gene polymorphism; Genetic analysis; Genetic aspects; Genetic factors; Genetic Markers; Health aspects; Heart; Humans; Inflammation; Inflammation - genetics; Logistic Models; Medical sciences; p53 Protein; Polymorphism, Genetic - genetics; Predictive Value of Tests; Prospective Studies; Recurrence; Restenosis; Risk Assessment; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Stenosis; Stents; Transluminal angioplasty; Tumor necrosis factor; Tumor necrosis factor receptors; United States; Human; Angioplasty; Coronary artery; Stenosis; Cardiovascular disease; Genotype; Coronary heart disease; Artery; Arterial disease; Vascular disease; Restenosis; Gene; Risk factor; Predisposition; Complication; Genetics; Single nucleotide polymorphism
• ISSN: 1470-269X; 1466-4860; 1473-1150
• DOI: 10.1038/sj.tpj.6500101

The complexity of recognizing the potential contribution of a number of possible predictors of complex disorders is increasingly challenging with the application of large-scale single nucleotide polymorphism (SNP) typing. In the search for putative genetic factors predisposing to coronary artery restenosis following balloon angioplasty, we determined genotypes for 94 SNPs representing 62 candidate genes, in a prospectively assembled cohort of 342 cases and 437 controls. Using a customized coupled-logistic regression procedure accounting for both additive and interactive effects, we identified seven SNPs in seven genes that, together, showed a statistically significant association with restenosis incidence (P <0.0001), accounting for 11.6% of overall variance observed. Among them are candidate genes for cardiovascular pathophysiology (apolipoprotein-species and NOS), inflammatory response (TNF receptor and CD14), and cell-cycle control (p53 and p53-associated protein). Our results emphasize the need to account for complex multi-gene influences and interactions when assessing the molecular pathology of multifactorial medical entities.