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 - Doevendans, Pieter A. F. M.
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
PY - 2011
Y1 - 2011
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
U2 - https://doi.org/10.1093/hmg/ddr389
DO - https://doi.org/10.1093/hmg/ddr389
M3 - Article
C2 - 21878436
SN - 0964-6906
VL - 20
SP - 4748
EP - 4757
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 23
ER -