TY - JOUR
T1 - Assessment of the 9p21.3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes
AU - Rivera, Natalia V.
AU - Carreras-Torres, Robert
AU - Roncarati, Roberta
AU - Viviani-Anselmi, Chiara
AU - De Micco, Francesca
AU - Mezzelani, Alessandra
AU - Koch, Werner
AU - Hoppmann, Petra
AU - Kastrati, Adnan
AU - Stewart, Alexandre F.R.
AU - Chen, Li
AU - Roberts, Robert
AU - Karssen, Lennart C.
AU - Amin, Najaf
AU - Trimarco, Valentina
AU - Izzo, Raffaele
AU - Iaccarino, Guido
AU - Condorelli, Gerolama
AU - Puca, Annibale A.
AU - Pagnotta, Paolo
AU - Airoldi, Flavio
AU - Trimarco, Bruno
AU - van Duijn, Cornelia M.
AU - Condorelli, Gianluigi
AU - Briguori, Carlo
N1 - Funding Information:
Italian Population Study – This study was supported by grants from the Italian Ministry of Health and Research (MIUR), Italian Ministry of Health and Region of Lombardy to GC. Imputations were carried out on the Genetic Cluster Computer (www.geneticcluster.org) which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Canadian Population Study – The Ottawa Heart genomics Study was supported by the Canada Foundation for Innovation and the Ontario Research Fund. German Population Study – This study was funded by an institutional grant from the Deutsches Herzzentrum München. We thank Dr. John Bruce Cantrell and Dr. Michael Latronico for the nice and kind editing of this work.
PY - 2013/1/23
Y1 - 2013/1/23
N2 - 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.
AB - 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.
KW - 9p21.3
KW - Coronary artery disease
KW - Diabetes mellitus
KW - Genetics
KW - Severity of CAD
KW - Single nucleotide polymorphism
KW - T2D
UR - http://www.scopus.com/inward/record.url?scp=84872591785&partnerID=8YFLogxK
U2 - 10.1186/1471-2350-14-11
DO - 10.1186/1471-2350-14-11
M3 - Article
C2 - 23343465
AN - SCOPUS:84872591785
SN - 1471-2350
VL - 14
JO - BMC Medical Genetics
JF - BMC Medical Genetics
IS - 1
M1 - 11
ER -
