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

BMC Medical Genetics

Carlo Briguori⁴  Gianluigi Condorelli^1,12  Cornelia M van Duijn⁵  Bruno Trimarco⁶  Flavio Airoldi^1,10  Paolo Pagnotta⁹  Annibale A Puca^1,11  Gerolama Condorelli¹  Guido Iaccarino^1,11  Raffaele Izzo⁶  Valentina Trimarco²  Najaf Amin⁵  Lennart C Karssen⁵  Robert Roberts⁸  Li Chen⁸  Alexandre FR Stewart⁸  Adnan Kastrati^1,13  Petra Hoppmann^1,13  Werner Koch^1,13  Alessandra Mezzelani⁷  Francesca De Micco^1,10  Chiara Viviani-Anselmi^1,10  Roberta Roncarati^1,12  Robert Carreras-Torres³  Natalia V Rivera^1,10 

[1]Department of Biology, Cellular and Molecular Pathology, University Federico II, Naples, Italy

[2]Department of Neuroscience, Federico II University, Federico II University Hospital, Naples, Italy

[3]Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain

[4]Laboratory of Interventional Cardiology, Department of Cardiology, Clinica Meditterranea of Naples, Via Orazio 2, 80121, Naples, Italy

[5]Department of Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands

[6]Department of Clinical Medicine and Cardiovascular Sciences, Federico II University Hospital, Naples, Italy

[7]Institute of Biomedical Technologies (ITB), National Research Council (CNR), Milan, Italy

[8]Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Canada

[9]Humanitas Clinical and Research Center, Milan, Rozzano, Italy

[10]IRCCS Multimedica, Via Fantoli 16/15, 20138, Milan, Italy

[11]School of Medicine, University of Salerno, Baronissi, Salerno, Italy

[12]Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR), Milan, Italy

[13]Deutsches Herzzentrum München, Munich, Germany

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

Others  :  1177744
DOI  :  10.1186/1471-2350-14-11

 received in 2012-03-30, accepted in 2012-10-22,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Rivera et al.; licensee BioMed Central Ltd.

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