title: Genetic and clinical correlates of early-outgrowth colony-forming units.
abstract: BACKGROUND
  Several bone marrow-derived cell populations may have angiogenic activity, including cells termed endothelial progenitor cells. Decreased numbers of circulating angiogenic cell populations have been associated with increased cardiovascular risk. However, few data exist from large, unselected samples, and the genetic determinants of these traits are unclear.
  
  
  RESULTS
  We examined the clinical and genetic correlates of early-outgrowth colony-forming units (CFUs) in 1799 participants of the Framingham Heart Study (mean age, 66 years; 54% women). Among individuals without cardiovascular disease (n = 1612), CFU number was inversely related to advanced age (P = 0.004), female sex (P = 0.04), and triglycerides (P = 0.008) and positively related to hormone replacement (P = 0.008) and statin therapy (P = 0.027) in stepwise multivariable analyses. Overall, CFU number was inversely related to the Framingham risk score (P = 0.01) but not with prevalent cardiovascular disease. In genome-wide association analyses in the entire sample, polymorphisms were associated with CFUs at the MOSC1 locus (P = 3.3 × 10(-7)) and at the SLC22A3-LPAL2-LPA locus (P = 4.9 × 10(-7)), a previously replicated susceptibility locus for myocardial infarction. Furthermore, alleles at the SLC22A3-LPAL2-LPA locus that were associated with decreased CFUs were also related to increased risk of myocardial infarction (P = 1.1 × 10(-4)).
  
  
  CONCLUSIONS
  In a community-based sample, early-outgrowth CFUs are inversely associated with select cardiovascular risk factors. Furthermore, genetic variants at the SLC22A3-LPAL2-LPA locus are associated with both decreased CFUs and an increased risk of myocardial infarction. These findings are consistent with the hypothesis that decreased circulating angiogenic cell populations promote susceptibility to myocardial infarction.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Stanley Y
authors.initials: SY
authors.lastname: Shaw
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: McCabe
authors.forename: Julius S
authors.initials: JS
authors.lastname: Ngwa
authors.forename: Ying A
authors.initials: YA
authors.lastname: Wang
authors.forename: Roderick P
authors.initials: RP
authors.lastname: Martin
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Klein
authors.forename: Basma
authors.initials: B
authors.lastname: Hashmi
authors.forename: Olujimi A
authors.initials: OA
authors.lastname: Ajijola
authors.forename: Evan
authors.initials: E
authors.lastname: Lau
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Cohen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013234:Stem Cells / Q000166:cytology / Q000502:physiology