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| Original Article |
| Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease |
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| R Y L Zee1,a, J Hoh2,a, S Cheng3, R Reynolds3, M A Grow3, A Silbergleit3, K Walker3, L Steiner3, G Zangenberg3, A Fernandez-Ortiz4, C Macaya4, E Pintor4, A Fernandez-Cruz4, J Ott2 and K Lindpainter1,5 |
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1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
2Laboratory of Statistical Genetics, Rockefeller University, New York, NY, USA
3Department of Human Genetics, Roche Molecular Systems, Alameda, CA, USA
4Hospital Universitario San Carlos, Ciudad Universitaria, Madrid, Spain
5F Hoffmann-La Roche Ltd, Basel, Switzerland
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Correspondence to: K Lindpainter, MD, MPH, VP Research, Director, Roche Genetics, F Hoffmann-La Roche, Bldg 93/532, CH-4070 Basel, Switzerland. Tel: +41-61-688.0254 Fax: +41-61-688.1929 E-mail: klaus.lindpaintner@roche.com | |
aContributed equally to the study |
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| Abstract |
| 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. The Pharmacogenomics Journal (2002) 2, 197-201. doi:10.1038/sj.tpj.6500101 |
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| Keywords |
| restenosis; angioplasty; SNPs; risk factors |
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| Received 6 December 2001; revised 21 February 2002; accepted 21 February 2002 |
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| 2002, Volume 2, Number 3, Pages 197-201 |
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