title: Polymorphism of the complement 5 gene and cardiovascular outcome in patients with atherosclerosis.
abstract: BACKGROUND
  Humoral mediators of inflammation, in particular the complement system, have been described to play an important role in atherogenesis. Previously, we found a single-nucleotide polymorphism (SNP) in the complement 5 gene (C5 rs17611, A>G) independently associated with stroke. Up to now, the impact of C5 rs17611 on the progression of atherosclerosis and cardiovascular outcome in patients with asymptomatic atherosclerosis was unclear.
  
  
  METHODS
  We investigated C5 rs17611 in a cohort of 1065 consecutive patients with asymptomatic carotid atherosclerosis. All patients were prospectively followed for the progression of carotid atherosclerosis and the development of a first major cardiovascular event (MACE), respectively.
  
  
  RESULTS
  Three hundred and thirty-seven patients (31·6%) experienced a MACE during a median follow-up of 3·0 years. The homozygous GG genotype of the C5 rs17611 was significantly associated with adverse cardiovascular outcome (adjusted HR: 1·36 [95% CI, 1·07-1·73]; P = 0·01). After stratification for sex, C5 rs17611 CC was found to be an independent risk factor for MACE in men (HR 1·50 [95% CI, 1·12-1·83]). No association of C5 rs17611 with progression of carotid stenosis, observed in 93 (8·7%) patients, was detectable. Performance of ELISA indicated a significant association of the C5 rs17611 variant with C5a plasma levels.
  
  
  CONCLUSIONS
  The C5 rs17611 GG genotype is associated with increased C5a plasma levels and represents a risk factor for adverse cardiovascular outcome in male patients with carotid atherosclerosis.
authors.affiliation: Department of Internal Medicine II, Division of Angiology, Medical University Vienna, Vienna, Austria. matthias.hoke@meduniwien.ac.at
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoke
authors.forename: Walter
authors.initials: W
authors.lastname: Speidl
authors.forename: Martin
authors.initials: M
authors.lastname: Schillinger
authors.forename: Erich
authors.initials: E
authors.lastname: Minar
authors.forename: Sonja
authors.initials: S
authors.lastname: Zehetmayer
authors.forename: Michael
authors.initials: M
authors.lastname: Schönherr
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics; D015331:Cohort Studies; D003182:Complement C5 / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D003182:Complement C5