Document Detail


A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts.
MedLine Citation:
PMID:  23312942     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Michael S Conte; Christopher D Owens; Michael Belkin; Mark A Creager; Karen L Edwards; Warren J Gasper; Richard D Kenagy; Renee C LeBoeuf; Michael Sobel; Alexander Clowes
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural     Date:  2013-01-09
Journal Detail:
Title:  Journal of vascular surgery     Volume:  57     ISSN:  1097-6809     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-06-17     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1179-85.e1-2     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Society for Vascular Surgery. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Aged
Critical Illness
Cyclin-Dependent Kinase Inhibitor p27 / genetics*
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Graft Occlusion, Vascular / genetics*,  physiopathology,  ultrasonography
Humans
Intermittent Claudication / genetics,  physiopathology,  surgery*
Ischemia / genetics,  physiopathology,  surgery*
Lower Extremity / blood supply*
Male
Middle Aged
Multivariate Analysis
Peripheral Arterial Disease / genetics,  physiopathology,  surgery*
Phenotype
Polymorphism, Single Nucleotide*
Promoter Regions, Genetic
Proportional Hazards Models
Retrospective Studies
Risk Factors
Time Factors
Treatment Outcome
Ultrasonography, Doppler, Duplex
United States
Vascular Grafting / adverse effects*
Vascular Patency / genetics*
Veins / physiopathology,  transplantation*,  ultrasonography
Grant Support
ID/Acronym/Agency:
HL098227/HL/NHLBI NIH HHS; HL30946/HL/NHLBI NIH HHS; HL75771/HL/NHLBI NIH HHS; R01 HL030946/HL/NHLBI NIH HHS; R01 HL075771/HL/NHLBI NIH HHS; R01 HL098227/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1B protein, human; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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