OBJECTIVE: Factors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27(Kip1) gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency. METHODS: This was a retrospective genetic association study nested within a prospective cohort of 204 patients from three referral centers undergoing LEVBG for claudication or critical ischemia. The main outcome measure was primary vein graft patency. RESULTS: All patients were followed up for a minimum of 1 year with duplex graft surveillance (median follow-up, 893 days; interquartile range, 539-1315). Genomic DNA was isolated and SNP analysis for the p27(Kip1)-838C>A variants was performed. Allele frequencies were correlated with graft outcome using survival analysis and Cox proportional hazards modeling. The p27(Kip1)-838C>A allele frequencies observed were CA, 53%; CC, 30%; and AA, 17%, satisfying Hardy-Weinberg equilibrium. Race (P = .025) and history of coronary artery disease (P = .027) were different across the genotypes; all other baseline variables were similar. Primary graft patency was greater among patients with the -838AA genotype (75% AA vs 55% CA/CC at 3 years; P = .029). In a Cox proportional hazards model including age, sex, race, diabetes, critical limb ischemia, redo (vs primary) bypass, vein type, and baseline C-reactive protein level, the p27(Kip1)-838AA genotype was significantly associated with higher graft patency (hazard ratio for failure, 0.4; 95% confidence interval, 0.17-0.93). Genotype was also associated with early (0-1 month) changes in graft lumen diameter by ultrasound imaging. CONCLUSIONS: These data suggest that the p27(Kip1)-838C>A SNP is associated with LEVBG patency and, together with previous reports, underscore a central role for p27(Kip1) in the generic response to vascular injury.
OBJECTIVE: Factors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27(Kip1) gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency. METHODS: This was a retrospective genetic association study nested within a prospective cohort of 204 patients from three referral centers undergoing LEVBG for claudication or critical ischemia. The main outcome measure was primary vein graft patency. RESULTS: All patients were followed up for a minimum of 1 year with duplex graft surveillance (median follow-up, 893 days; interquartile range, 539-1315). Genomic DNA was isolated and SNP analysis for the p27(Kip1)-838C>A variants was performed. Allele frequencies were correlated with graft outcome using survival analysis and Cox proportional hazards modeling. The p27(Kip1)-838C>A allele frequencies observed were CA, 53%; CC, 30%; and AA, 17%, satisfying Hardy-Weinberg equilibrium. Race (P = .025) and history of coronary artery disease (P = .027) were different across the genotypes; all other baseline variables were similar. Primary graft patency was greater among patients with the -838AA genotype (75% AA vs 55% CA/CC at 3 years; P = .029). In a Cox proportional hazards model including age, sex, race, diabetes, critical limb ischemia, redo (vs primary) bypass, vein type, and baseline C-reactive protein level, the p27(Kip1)-838AA genotype was significantly associated with higher graft patency (hazard ratio for failure, 0.4; 95% confidence interval, 0.17-0.93). Genotype was also associated with early (0-1 month) changes in graft lumen diameter by ultrasound imaging. CONCLUSIONS: These data suggest that the p27(Kip1)-838C>A SNP is associated with LEVBG patency and, together with previous reports, underscore a central role for p27(Kip1) in the generic response to vascular injury.
Authors: Scott A Berceli; Nathanael D Hevelone; Stuart R Lipsitz; Dennis F Bandyk; Alexander W Clowes; Gregory L Moneta; Michael S Conte Journal: J Vasc Surg Date: 2007-10-22 Impact factor: 4.268
Authors: John H Alexander; Gail Hafley; Robert A Harrington; Eric D Peterson; T Bruce Ferguson; Todd J Lorenz; Abhinav Goyal; Michael Gibson; Michael J Mack; Daniel Gennevois; Robert M Califf; Nicholas T Kouchoukos Journal: JAMA Date: 2005-11-16 Impact factor: 56.272
Authors: Louis L Nguyen; Michael S Conte; Matthew T Menard; Edwin C Gravereaux; David K Chew; Magruder C Donaldson; Anthony D Whittemore; Michael Belkin Journal: J Vasc Surg Date: 2004-11 Impact factor: 4.268
Authors: Christopher D Owens; Paul M Ridker; Michael Belkin; Allen D Hamdan; Frank Pomposelli; Frank Logerfo; Mark A Creager; Michael S Conte Journal: J Vasc Surg Date: 2006-11-21 Impact factor: 4.268
Authors: Michael S Conte; Dennis F Bandyk; Alexander W Clowes; Gregory L Moneta; Lynn Seely; Todd J Lorenz; Hamid Namini; Allen D Hamdan; Sean P Roddy; Michael Belkin; Scott A Berceli; Richard J DeMasi; Russell H Samson; Scott S Berman Journal: J Vasc Surg Date: 2006-04 Impact factor: 4.268
Authors: Alexandre C Pereira; Ayumi A Miyakawa; Neuza H M Lopes; Paulo R Soares; Sergio A de Oliveira; Luiz A M Cesar; Jose F Ramires; Whady Hueb; Jose Eduardo Krieger Journal: Thromb Res Date: 2007-07-02 Impact factor: 3.944
Authors: Richard D Kenagy; Mete Civelek; Shinsuke Kikuchi; Lihua Chen; Anthony Grieff; Michael Sobel; Aldons J Lusis; Alexander W Clowes Journal: J Vasc Surg Date: 2015-04-30 Impact factor: 4.268
Authors: Richard D Kenagy; Shinsuke Kikuchi; Lihua Chen; Errol S Wijelath; Andrew B Stergachis; John Stamatoyannopoulos; Gale L Tang; Alexander W Clowes; Michael Sobel Journal: J Vasc Surg Date: 2017-05-16 Impact factor: 4.268
Authors: Michael Sobel; Shinsuke Kikuchi; Lihua Chen; Gale L Tang; Tom N Wight; Richard D Kenagy Journal: J Vasc Surg Date: 2018-06-15 Impact factor: 4.268
Authors: Daniel Y Lu; Elizabeth Y Chen; Daniel J Wong; Kota Yamamoto; Clinton D Protack; Willis T Williams; Roland Assi; Michael R Hall; Nirvana Sadaghianloo; Alan Dardik Journal: J Surg Res Date: 2014-01-30 Impact factor: 2.192
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: Dan Yu; George Makkar; Tuo Dong; Dudley K Strickland; Rajabrata Sarkar; Thomas Stacey Monahan Journal: PLoS One Date: 2015-11-03 Impact factor: 3.240