TY - JOUR
T1 - A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention
AU - Sampietro, M. Lourdes
AU - Trompet, Stella
AU - Verschuren, Jeffrey J.W.
AU - Talens, Rudolf P.
AU - Deelen, Joris
AU - Heijmans, Bastiaan T.
AU - de Winter, Robbert J.
AU - Tio, Rene A.
AU - Pieter, Pieter A.F.
AU - Ganesh, Santhi K.
AU - Nabel, Elizabeth G.
AU - Westra, Harm Jan
AU - Franke, Lude
AU - van den Akker, Erik B.
AU - Westendorp, Rudi G.J.
AU - Zwinderman, Aeilko H.
AU - Kastrati, Adnan
AU - Koch, Werner
AU - Slagboom, P. Eline
AU - de Knijff, Peter
AU - Jukema, J. Wouter
N1 - Funding Information:
This work was supported by grants from the Interuniversity Cardiology Institute of the Netherlands (ICIN) and the Durrer Center for Cardiogenetic Research both Institutes of the Netherlands Royal Academy of Arts and Sciences (KNAW), the Netherlands Heart Foundation, the Center for Medical Systems Biology (CMSB), a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NWO), the Netherlands Consortium for Healthy Ageing (NCHA) and the EU project HEALTH-F2-2007 223004 PHASE. J.W.J. is an established clinical investigator of the Netherlands Heart Foundation (2001D032). Part of this project was funded by a grant from the Netherlands Genomics Initiative (NGI) and Netherlands Organization for Scientific Research (NWO) within the frame-work of the Forensic Genomics Consortium Netherlands (FGCN) to P.d.K. CardioGene was funded in part by the National Heart, Lung and Blood Institute Division of Intramural Research. S.K.G. was supported in part by NHLBI R00HL089413. The funders had no role in study design, data collection and analysis, decision to publish or the preparation of the manuscript.
PY - 2011/12
Y1 - 2011/12
N2 - Percutaneous coronary intervention (PCI) has become an effective therapy to treat obstructive coronary artery diseases (CAD). However, one of the major drawbacks of PCI is the occurrence of restenosis in 5-25% of all initially treated patients. Restenosis is defined as the re-narrowing of the lumen of the blood vessel, resulting in renewed symptoms and the need for repeated intervention. To identify genetic variants that are associated with restenosis, a genome-wide association study (GWAS) was conducted in 295 patients who developed restenosis (cases) and 571 who did not (controls) from the GENetic Determinants of Restenosis (GENDER) study. Analysis of ~ 550 000 single nucleotide polymorphisms (SNPs) in GENDER was followed by a replication phase in three independent case-control populations (533 cases and 3067 controls). A potential susceptibility locus for restenosis at chromosome 12, including rs10861032 (P combined = 1.11 × 10 -7) and rs9804922 (P combined = 1.45 × 10 -6), was identified in the GWAS and replication phase. In addition, both SNPs were also associated with coronary events (rs10861032, P additive = 0.005; rs9804922, P additive = 0.023) in a trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER) and all-cause mortality in PROSPER (rs10861032, P additive = 0.007; rs9804922, P additive = 0.013) and GENDER (rs10861032, P additive = 0.005; rs9804922, P additive = 0.023). Further analysis suggests that this locus could be involved in regulatory functions.
AB - Percutaneous coronary intervention (PCI) has become an effective therapy to treat obstructive coronary artery diseases (CAD). However, one of the major drawbacks of PCI is the occurrence of restenosis in 5-25% of all initially treated patients. Restenosis is defined as the re-narrowing of the lumen of the blood vessel, resulting in renewed symptoms and the need for repeated intervention. To identify genetic variants that are associated with restenosis, a genome-wide association study (GWAS) was conducted in 295 patients who developed restenosis (cases) and 571 who did not (controls) from the GENetic Determinants of Restenosis (GENDER) study. Analysis of ~ 550 000 single nucleotide polymorphisms (SNPs) in GENDER was followed by a replication phase in three independent case-control populations (533 cases and 3067 controls). A potential susceptibility locus for restenosis at chromosome 12, including rs10861032 (P combined = 1.11 × 10 -7) and rs9804922 (P combined = 1.45 × 10 -6), was identified in the GWAS and replication phase. In addition, both SNPs were also associated with coronary events (rs10861032, P additive = 0.005; rs9804922, P additive = 0.023) in a trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER) and all-cause mortality in PROSPER (rs10861032, P additive = 0.007; rs9804922, P additive = 0.013) and GENDER (rs10861032, P additive = 0.005; rs9804922, P additive = 0.023). Further analysis suggests that this locus could be involved in regulatory functions.
UR - http://www.scopus.com/inward/record.url?scp=81255209178&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddr389
DO - 10.1093/hmg/ddr389
M3 - Article
C2 - 21878436
AN - SCOPUS:81255209178
SN - 0964-6906
VL - 20
SP - 4748
EP - 4757
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 23
M1 - ddr389
ER -