Genetic and clinical correlates of early-outgrowth colony-forming units.

Shaw SY, Cheng S, Cupples LA, Larson MG, McCabe EL, Ngwa JS, Wang YA, Martin RP, Klein RJ, Hashmi B, Ajijola OA, Lau E, O'Donnell CJ, Vasan RS, Cohen KS, Wang TJ
Circ Cardiovasc Genet. 2011 4 (3): 296-304

PMID: 21493818 · PMCID: PMC3339257 · DOI:10.1161/CIRCGENETICS.110.958470

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.

METHODS AND 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.

MeSH Terms (11)

Aged Bone Marrow Cells Cardiovascular Diseases Endothelial Cells Female Humans Male Middle Aged Polymorphism, Single Nucleotide Risk Factors Stem Cells

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