BACKGROUND: Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal factor in restenosis. Association studies have identified genes that may predispose to restenosis, but confirmation by large prospective studies is lacking. Our aim was to identify polymorphisms and haplotypes in genes involved in inflammatory pathways that predispose to restenosis. METHODS AND RESULTS: The GENetic DEterminants of Restenosis (GENDER) project is a multicenter prospective study, including 3104 consecutive patients after successful PCI. Forty-eight polymorphisms in 34 genes in pathways possibly involved in the inflammatory process were analyzed. The 16Gly variant of the beta2-adrenergic receptor gave an increased risk of target vessel revascularization (TVR). The rare alleles of the CD14 gene (-260T/T), colony-stimulating factor 2 gene (117Thr/Thr), and eotaxin gene (-1328A/A) were associated with decreased risk of TVR. However, through the use of multiple testing corrections with permutation analysis, the probability of finding 4 significant markers by chance was 12%. CONCLUSIONS: Polymorphisms in 4 genes considered involved in the inflammatory reaction showed an association with TVR after PCI. Our results may contribute to the unraveling of the restenotic process. Given the explorative nature of this analysis, our results need to be replicated in other studies.
BACKGROUND:Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal factor in restenosis. Association studies have identified genes that may predispose to restenosis, but confirmation by large prospective studies is lacking. Our aim was to identify polymorphisms and haplotypes in genes involved in inflammatory pathways that predispose to restenosis. METHODS AND RESULTS: The GENetic DEterminants of Restenosis (GENDER) project is a multicenter prospective study, including 3104 consecutive patients after successful PCI. Forty-eight polymorphisms in 34 genes in pathways possibly involved in the inflammatory process were analyzed. The 16Gly variant of the beta2-adrenergic receptor gave an increased risk of target vessel revascularization (TVR). The rare alleles of the CD14 gene (-260T/T), colony-stimulating factor 2 gene (117Thr/Thr), and eotaxin gene (-1328A/A) were associated with decreased risk of TVR. However, through the use of multiple testing corrections with permutation analysis, the probability of finding 4 significant markers by chance was 12%. CONCLUSIONS: Polymorphisms in 4 genes considered involved in the inflammatory reaction showed an association with TVR after PCI. Our results may contribute to the unraveling of the restenotic process. Given the explorative nature of this analysis, our results need to be replicated in other studies.
Authors: Sandrin C Bergheanu; Douwe Pons; Bas L van der Hoeven; Su-San Liem; Bob Siegerink; Martin J Schalij; Johanna G van der Bom; J Wouter Jukema Journal: Heart Vessels Date: 2010-10-30 Impact factor: 2.037
Authors: M Lourdes Sampietro; Stella Trompet; Jeffrey J W Verschuren; Rudolf P Talens; Joris Deelen; Bastiaan T Heijmans; Robbert J de Winter; Rene A Tio; Pieter A F M Doevendans; Santhi K Ganesh; Elizabeth G Nabel; Harm-Jan Westra; Lude Franke; Erik B van den Akker; Rudi G J Westendorp; Aeilko H Zwinderman; Adnan Kastrati; Werner Koch; P Eline Slagboom; Peter de Knijff; J Wouter Jukema Journal: Hum Mol Genet Date: 2011-08-30 Impact factor: 6.150
Authors: Margreet R de Vries; Karin H Simons; J Wouter Jukema; Jerry Braun; Paul H A Quax Journal: Nat Rev Cardiol Date: 2016-05-19 Impact factor: 32.419
Authors: Zuobiao Yuan; Hong Pei; Drew J Roberts; Zhimin Zhang; Jessica S Rowlan; Alan H Matsumoto; Weibin Shi Journal: Circ Cardiovasc Genet Date: 2009-06