|A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts.|
|PMID: 23312942 Owner: NLM Status: MEDLINE|
|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.
|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|
|Type: Journal Article; Multicenter Study; Research Support, N.I.H., Extramural Date: 2013-01-09|
|Title: Journal of vascular surgery Volume: 57 ISSN: 1097-6809 ISO Abbreviation: J. Vasc. Surg. Publication Date: 2013 May|
|Created Date: 2013-04-22 Completed Date: 2013-06-17 Revised Date: 2014-09-19|
Medline Journal Info:
|Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: United States|
|Languages: eng Pagination: 1179-85.e1-2 Citation Subset: IM|
|Copyright © 2013 Society for Vascular Surgery. All rights reserved.|
|APA/MLA Format Download EndNote Download BibTex|
Cyclin-Dependent Kinase Inhibitor p27 / genetics*
Genetic Association Studies
Genetic Predisposition to Disease
Graft Occlusion, Vascular / genetics*, physiopathology, ultrasonography
Intermittent Claudication / genetics, physiopathology, surgery*
Ischemia / genetics, physiopathology, surgery*
Lower Extremity / blood supply*
Peripheral Arterial Disease / genetics, physiopathology, surgery*
Polymorphism, Single Nucleotide*
Promoter Regions, Genetic
Proportional Hazards Models
Ultrasonography, Doppler, Duplex
Vascular Grafting / adverse effects*
Vascular Patency / genetics*
Veins / physiopathology, transplantation*, ultrasonography
|HL098227/HL/NHLBI NIH HHS; HL30946/HL/NHLBI NIH HHS; HL75771/HL/NHLBI NIH HHS; P30 DK017047/DK/NIDDK NIH HHS; R01 HL030946/HL/NHLBI NIH HHS; R01 HL075771/HL/NHLBI NIH HHS; R01 HL098227/HL/NHLBI NIH HHS|
|0/CDKN1B protein, human; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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