Abstract
BackgroundCoronary restenosis after percutaneous coronary intervention still remains a significant problem, despite all medical advances. Unraveling the mechanisms leading to restenosis development remains challenging. Many studies have identified genetic markers associated with restenosis, but consistent replication of the reported markers is scarce. The aim of the current study was to analyze the joined effect of previously in literature reported candidate genes for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank.Methodology/Principal FindingsCandidate genes were selected using a MEDLINE search including the terms ‘genetic polymorphism’ and ‘coronary restenosis’. The final set included 36 genes. Subsequently, all single nucleotide polymorphisms (SNPs) in the genomic region of these genes were analyzed in GENDER using set-based analysis in PLINK. The GENDER databank contains genotypic data of 2,571,586 SNPs of 295 cases with restenosis and 571 matched controls. The set, including all 36 literature reported genes, was, indeed, significantly associated with restenosis, p = 0.024 in the GENDER study. Subsequent analyses of the individual genes demonstrated that the observed association of the complete set was determined by 6 of the 36 genes.ConclusionDespite overt inconsistencies in literature, with regard to individual candidate gene studies, this is the first study demonstrating that the joint effect of all these genes together, indeed, is associated with restenosis.
Highlights
Restenosis is a complex disease for which the causative mechanisms have not yet been fully identified
Restenosis still remains a significant complication after percutaneous coronary intervention (PCI).[1]
Over the last decades genetic research has developed from candidate gene approaches [3,4,5] to multiplex arrays [6] and to genome wide association studies (GWAS).[7]
Summary
Restenosis is a complex disease for which the causative mechanisms have not yet been fully identified. Restenosis still remains a significant complication after percutaneous coronary intervention (PCI).[1] Identification of risk factors and underlying mechanisms could be useful in risk stratification of patients, they contribute to our understanding of this condition. These factors could provide evidence on which to base individually tailored treatment and aid in the development of novel therapeutic modalities.[2] Unraveling the mechanisms leading to restenosis development remains challenging. The aim of the current study was to analyze the joined effect of previously in literature reported candidate genes for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank
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