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Circulating CD34(+) progenitor cell frequency is associated with clinical and genetic factors.

Cohen KS, Cheng S, Larson MG, Cupples LA, McCabe EL, Wang YA, Ngwa JS, Martin RP, Klein RJ, Hashmi B, Ge Y, O'Donnell CJ, Vasan RS, Shaw SY, Wang TJ
Blood. 2013 121 (8): e50-6

PMID: 23287867 · PMCID: PMC3578962 · DOI:10.1182/blood-2012-05-424846

Circulating blood CD34(+) cells consist of hematopoietic stem/progenitor cells, angiogenic cells, and endothelial cells. In addition to their clinical use in hematopoietic stem cell transplantation, CD34(+) cells may also promote therapeutic neovascularization. Therefore, understanding the factors that influence circulating CD34(+) cell frequency has wide implications for vascular biology in addition to stem cell transplantation. In the present study, we examined the clinical and genetic characteristics associated with circulating CD34(+) cell frequency in a large, community-based sample of 1786 Framingham Heart Study participants.Among subjects without cardiovascular disease (n = 1595), CD34(+) frequency was inversely related to older age, female sex, and smoking. CD34(+) frequency was positively related to weight, serum total cholesterol, and statin therapy. Clinical covariates accounted for 6.3% of CD34(+) variability. CD34(+) frequency was highly heritable (h(2) = 54%; P < .0001). Genome-wide association analysis of CD34(+) frequency identified suggestive associations at several loci, including OR4C12 (chromosome 11; P = 6.7 × 10(-7)) and ENO1 and RERE (chromosome 1; P = 8.8 × 10(-7)). CD34(+) cell frequency is reduced in older subjects and is influenced by environmental factors including smoking and statin use. CD34(+) frequency is highly heritable. The results of the present study have implications for therapies that use CD34(+) cell populations and support efforts to better understand the genetic mechanisms that underlie CD34(+) frequency.

MeSH Terms (24)

Aged Antigens, CD34 Biomarkers, Tumor Cardiovascular Diseases Carrier Proteins Chromosomes, Human, Pair 1 Chromosomes, Human, Pair 11 DNA-Binding Proteins Female Genome-Wide Association Study Hematopoiesis Hematopoietic Stem Cells Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors Male Massachusetts Middle Aged Oligonucleotide Array Sequence Analysis Phosphopyruvate Hydratase Prevalence Risk Factors Sex Distribution Smoking Tumor Suppressor Proteins

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