TY - JOUR
T1 - Circulating CD34+ progenitor cell frequency is associated with clinical and genetic factors
AU - Cohen, Kenneth S.
AU - Cheng, Susan
AU - Larson, Martin G.
AU - Cupples, L. Adrienne
AU - McCabe, Elizabeth L.
AU - Wang, Ying A.
AU - Ngwa, Julius S.
AU - Martin, Roderick P.
AU - Klein, Rachael J.
AU - Hashmi, Basma
AU - Ge, Yin
AU - O'Donnell, Christopher J.
AU - Vasan, Ramachandran S.
AU - Shaw, Stanley Y.
AU - Wang, Thomas J.
PY - 2013/2/21
Y1 - 2013/2/21
N2 - 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 Framing-ham 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 (h2 = 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.
AB - 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 Framing-ham 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 (h2 = 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.
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U2 - 10.1182/blood-2012-05-424846
DO - 10.1182/blood-2012-05-424846
M3 - Article
C2 - 23287867
AN - SCOPUS:84874428676
SN - 0006-4971
VL - 121
SP - e50-e56
JO - Blood
JF - Blood
IS - 8
ER -