TY - JOUR
T1 - Genetic and clinical correlates of early-outgrowth colony-forming units
AU - Shaw, Stanley Y.
AU - Cheng, Susan
AU - Cupples, L. Adrienne
AU - Larson, Martin G.
AU - McCabe, Elizabeth L.
AU - Ngwa, Julius S.
AU - Wang, Ying A.
AU - Martin, Roderick P.
AU - Klein, Rachael J.
AU - Hashmi, Basma
AU - Ajijola, Olujimi A.
AU - Lau, Evan
AU - O'Donnell, Christopher J.
AU - Vasan, Ramachandran S.
AU - Cohen, Kenneth S.
AU - Wang, Thomas J.
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - Cardiovascular disease
KW - Cells
KW - Coronary disease
KW - Epidemiology
KW - Genetics
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UR - http://www.scopus.com/inward/citedby.url?scp=80052754144&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.110.958470
DO - 10.1161/CIRCGENETICS.110.958470
M3 - Article
C2 - 21493818
AN - SCOPUS:80052754144
SN - 1942-325X
VL - 4
SP - 296
EP - 304
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 3
ER -