期刊
BLOOD
卷 121, 期 8, 页码 E50-E56出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-05-424846
关键词
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类别
资金
- National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, R01-HL083197, R01-HL93328]
- National Institutes of Health [K99HL107642]
- Ellison Foundation
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 x 10(-7)) and ENO1 and RERE (chromosome 1; P = 8.8 x 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.
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