title: A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention.
abstract: 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.
authors: Department of Human Genetics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
authors: M Lourdes
authors: ML
authors: Sampietro
authors: Stella
authors: S
authors: Trompet
authors: Jeffrey J W
authors: JJ
authors: Verschuren
authors: Rudolf P
authors: RP
authors: Talens
authors: Joris
authors: J
authors: Deelen
authors: Bastiaan T
authors: BT
authors: Heijmans
authors: Robbert J
authors: RJ
authors: de Winter
authors: Rene A
authors: RA
authors: Tio
authors: Pieter A F M
authors: PA
authors: Doevendans
authors: Santhi K
authors: SK
authors: Ganesh
authors: Elizabeth G
authors: EG
authors: Nabel
authors: Harm-Jan
authors: HJ
authors: Westra
authors: Lude
authors: L
authors: Franke
authors: Erik B
authors: EB
authors: van den Akker
authors: Rudi G J
authors: RG
authors: Westendorp
authors: Aeilko H
authors: AH
authors: Zwinderman
authors: Adnan
authors: A
authors: Kastrati
authors: Werner
authors: W
authors: Koch
authors: P Eline
authors: PE
authors: Slagboom
authors: Peter
authors: P
authors: de Knijff
authors: J Wouter
authors: JW
authors: Jukema
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D023903:Coronary Restenosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics