title: Lipoprotein lipase gene polymorphisms and the risk of target vessel revascularization after percutaneous coronary intervention.
abstract: OBJECTIVE
  We sought to identify polymorphisms in genes that predispose to restenosis.
  
  
  BACKGROUND
  Variations in the lipoprotein lipase (LPL) gene have been implicated in a number of pathophysiologic conditions associated with coronary heart disease. The present study examines the impact of polymorphisms in the LPL gene on restenosis (defined by target vessel revascularization [TVR]) in a large patient population undergoing percutaneous coronary intervention (PCI). A mouse model for restenosis was used to further investigate LPL's role in restenosis.
  
  
  METHODS
  The GENetic DEterminants of Restenosis (GENDER) project is a multicenter, prospective study design that enrolled 3,104 consecutive patients after successful PCI. These patients were genotyped for four different LPL gene polymorphisms. In apolipoprotein E (ApoE)*3-Leiden transgenic mice, arterial messenger ribonucleic acid (mRNA) was used to assess LPL expression during a cuff-induced restenotic process.
  
  
  RESULTS
  Using multivariable analysis, carriers of the 447Ter allele of the LPL enzyme showed a lower risk of TVR compared with 447Ser homozygotes (p = 0.005). In the mouse model, LPL mRNA levels were increased 40-fold compared with control arteries at 6 h after cuff placement.
  
  
  CONCLUSIONS
  The LPL C/G polymorphism (Ser447Ter), resulting in a truncation of the two C-terminal amino acids of the mature LPL protein, appears to be an important protective factor for TVR in humans. The role of LPL in this process was further established in a mouse model, where LPL expression was very strongly up-regulated in the target arterial wall, suggesting a contribution of this lipolytic enzyme to restenosis. Possibly, LPL Ser447Ter genotyping may lead to better risk stratification and tailored therapy in the prevention of restenosis after PCI.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pascalle S
authors.initials: PS
authors.lastname: Monraats
authors.forename: Jamal S
authors.initials: JS
authors.lastname: Rana
authors.forename: Melchior C
authors.initials: MC
authors.lastname: Nierman
authors.forename: Nuno M M
authors.initials: NM
authors.lastname: Pires
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.forename: Saskia Z H
authors.initials: SZ
authors.lastname: Rittersma
authors.forename: Abbey
authors.initials: A
authors.lastname: Schepers
authors.forename: Pieter A F
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
authors.forename: René A
authors.initials: RA
authors.lastname: Tio
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
authors.forename: Ernst E
authors.initials: EE
authors.lastname: van der Wall
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D023903:Coronary Restenosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D008071:Lipoprotein Lipase