Open Access Highly Accessed Research article

Assessment of the 9p21.3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes

Natalia V Rivera1*, Robert Carreras-Torres2, Roberta Roncarati13, Chiara Viviani-Anselmi1, Francesca De Micco1, Alessandra Mezzelani4, Werner Koch5, Petra Hoppmann5, Adnan Kastrati5, Alexandre FR Stewart6, Li Chen6, Robert Roberts6, Lennart C Karssen7, Najaf Amin7, Valentina Trimarco8, Raffaele Izzo9, Guido Iaccarino110, Gerolama Condorelli11, Annibale A Puca110, Paolo Pagnotta12, Flavio Airoldi1, Bruno Trimarco9, Cornelia M van Duijn7, Gianluigi Condorelli123 and Carlo Briguori13

Author Affiliations

1 IRCCS Multimedica, Via Fantoli 16/15, 20138, Milan, Italy

2 Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain

3 Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR), Milan, Italy

4 Institute of Biomedical Technologies (ITB), National Research Council (CNR), Milan, Italy

5 Deutsches Herzzentrum München, Munich, Germany

6 Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Canada

7 Department of Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands

8 Department of Neuroscience, Federico II University, Federico II University Hospital, Naples, Italy

9 Department of Clinical Medicine and Cardiovascular Sciences, Federico II University Hospital, Naples, Italy

10 School of Medicine, University of Salerno, Baronissi, Salerno, Italy

11 Department of Biology, Cellular and Molecular Pathology, University Federico II, Naples, Italy

12 Humanitas Clinical and Research Center, Milan, Rozzano, Italy

13 Laboratory of Interventional Cardiology, Department of Cardiology, Clinica Meditterranea of Naples, Via Orazio 2, 80121, Naples, Italy

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BMC Medical Genetics 2013, 14:11  doi:10.1186/1471-2350-14-11

Published: 23 January 2013

Abstract

Background

The 9p21.3 locus is strongly associated with the risk of coronary artery disease (CAD) and with type 2 diabetes (T2D). We investigated the association of 9p21.3 variants with severity of CAD (defined by the number of vessel diseased [VD]) in the presence and absence of T2D.

Methods

We tested 11 9p21.3-variants for association in a white Italian study (N = 2,908), and carried out replication in 2 independent white populations, a German study (N = 2,028) and a Canadian Study (N=950). SNP association and permutation analyses were conducted.

Results

We identified two 9p21.3-variants, rs4977574 (P < 4×10-4) and rs2383207 (P < 1.5×10-3) that were associated with severity of CAD in subjects without T2D. Association of rs4977574 with severity of CAD was confirmed in the Canadian Study. Results from subgroup analysis among patients with T2D showed an interaction between rs10738610 and T2D with P = 4.82×10-2. Further investigation showed that rs10738610 (P < 1.99×10-2) was found to be significantly associated with severity of CAD in subjects with T2D.

Conclusions

The 9p21.3 locus is significantly associated with severity of CAD. The number of associations of 9p21.3 variants with severity of CAD is variable to the presence and absence of T2D. In a CAD-susceptible region of 115 kb, there is only one variant associated with the severity of coronary vessel disease in the presence of type 2 diabetes.

Keywords:
Severity of CAD; Coronary artery disease; Diabetes mellitus; T2D; 9p21.3; Genetics; Single nucleotide polymorphism