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

The Pharmacogenomics Journal volume 2, pages 197–201 (2002)Cite this article

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.

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Acknowledgements

Supported by a Grant HG00008 from the National Institute of Health (JO), and a Research Development Award K04–HL–03138–01 from the National Heart, Lung, and Blood Institute (KL).

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Author notes

  1. R Y L Zee and J Hoh: Contributed equally to the study

Authors and Affiliations

  1. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    R Y L Zee & K Lindpainter

  2. Laboratory of Statistical Genetics, Rockefeller University, New York, NY, USA

    J Hoh & J Ott

  3. Department of Human Genetics, Roche Molecular Systems, Alameda, CA, USA

    S Cheng, R Reynolds, M A Grow, A Silbergleit, K Walker, L Steiner & G Zangenberg

  4. Hospital Universitario San Carlos, Ciudad Universitaria, Madrid, Spain

    A Fernandez-Ortiz, C Macaya, E Pintor & A Fernandez-Cruz

  5. F Hoffmann-La Roche Ltd, Basel, Switzerland

    K Lindpainter

Authors
  1. R Y L Zee
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  2. J Hoh
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  3. S Cheng
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  11. C Macaya
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  14. J Ott
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  15. K Lindpainter
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Correspondence to K Lindpainter.

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Zee, R., Hoh, J., Cheng, S. et al. Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease. Pharmacogenomics J 2, 197–201 (2002). https://doi.org/10.1038/sj.tpj.6500101

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  • DOI: https://doi.org/10.1038/sj.tpj.6500101

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