title: Can screening for genetic markers improve peripheral artery bypass patency?
abstract: OBJECTIVE
  Three genetic mutations have been associated with an increased risk of thromboembolic events: factor V Leiden R506Q, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T (MTHFR) mutations. The aim of this study was to determine the effect of these mutations on patency of peripheral bypass procedures and preoperative and postoperative thromboembolic events.
  
  
  METHODS
  Two hundred forty-four randomly selected volunteers participating in the Veterans Affairs Cooperative Study #362 were tested for factor V Leiden, prothrombin, or MTHFR mutations with polymerase chain reaction. Patients enrolled in the study were randomized to receive aspirin therapy or aspirin and warfarin therapy after a peripheral bypass procedure. The frequencies of preoperative and postoperative thromboembolic events and primary patency (PP), assisted primary patency (APP), and secondary patency (SP) rates were compared among carriers of the various mutations.
  
  
  RESULTS
  Fourteen patients (5.7%) were heterozygous for the factor V Leiden mutation, seven (2.9%) were heterozygous for the prothrombin mutation, and 108 (44.6%) were heterozygous and 15 (6.2%) homozygous for the MTHFR mutation. After surgery, patients homozygous for the MTHFR gene mutation had increased graft thrombosis, compared with patients who were heterozygous (33.3% versus 11.1%; P =.01), and lower PP, APP and SP rates (P <.05). Furthermore, patients heterozygous for the MTHFR mutation had fewer graft thromboses (11.1% versus 24.4%; P =.01), fewer below-knee amputations (0.9% versus 7.6%; P =.02), and higher PP, APP, and SP rates (PP, 79.6%; APP, 88.9%; SP, 90.7%; P <.05) compared with wild-type control subjects (PP, 63%; APP, 75.6%; SP, 76.5%; P <.05).
  
  
  CONCLUSIONS
  Patients with either factor V Leiden or prothrombin mutations were not at an increased risk for postoperative graft occlusion or thromboembolic events. Patients heterozygous for MTHFR mutation had a lower risk of graft thrombosis and higher graft patency rates compared with both homozygous and wild-type control subjects. Patients homozygous for the MTHFR mutation had lower graft patency rates compared with patients who were heterozygous, and a trend was seen toward lower patency rates compared with wild-type control subjects. Therefore, screening for the MTHFR gene mutation before surgery may identify patients at an increased risk of graft thrombosis.
authors.affiliation: Division of Vascular Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
authors.forename: Andrea L Cortese
authors.initials: AL
authors.lastname: Hassett
authors.forename: Frances
authors.initials: F
authors.lastname: McSherry
authors.forename: Philip
authors.initials: P
authors.lastname: Conner
authors.forename: Franklin A
authors.initials: FA
authors.lastname: Bontempo
authors.forename: William
authors.initials: W
authors.lastname: Williford
authors.forename: Willard
authors.initials: W
authors.lastname: Johnson
authors.forename: Michel S
authors.initials: MS
authors.lastname: Makaroun
mesh_terms: D000368:Aged; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D016491:Peripheral Vascular Diseases / Q000235:genetics* / Q000601:surgery*; D011183:Postoperative Complications; D011237:Predictive Value of Tests; D011897:Random Allocation; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology* / Q000235:genetics*; D014654:Vascular Patency / Q000235:genetics*; D014656:Vascular Surgical Procedures / Q000009:adverse effects*
chemical_list: D005819:Genetic Markers