1. Circulating CD34+ progenitor cell frequency is associated with clinical and genetic factors
- Author
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Stanley Y. Shaw, Rachael J. Klein, Yin Ge, Basma Hashmi, Ying A. Wang, Martin G. Larson, Susan Cheng, Ramachandran S. Vasan, Elizabeth L. McCabe, Christopher J. O'Donnell, Roderick P. Martin, Thomas J. Wang, Julius S. Ngwa, Kenneth S. Cohen, and L. Adrienne Cupples
- Subjects
Male ,medicine.medical_treatment ,Immunology ,CD34 ,Antigens, CD34 ,Genome-wide association study ,Hematopoietic stem cell transplantation ,Biology ,Biochemistry ,Framingham Heart Study ,Risk Factors ,Biomarkers, Tumor ,Prevalence ,medicine ,Humans ,Sex Distribution ,Progenitor cell ,Aged ,Oligonucleotide Array Sequence Analysis ,Transplantation ,Chromosomes, Human, Pair 11 ,Tumor Suppressor Proteins ,Smoking ,Cell Biology ,Hematology ,Middle Aged ,Hematopoietic Stem Cells ,Hematopoiesis ,DNA-Binding Proteins ,Haematopoiesis ,Massachusetts ,Cardiovascular Diseases ,Chromosomes, Human, Pair 1 ,Phosphopyruvate Hydratase ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Stem cell ,Carrier Proteins ,Genome-Wide Association Study - Abstract
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.
- Published
- 2013