title: Circulating CD34(+) progenitor cell frequency is associated with clinical and genetic factors.
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.
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. kcohen@medicine.bsd.uchicago.edu
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Cohen
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: McCabe
authors.forename: Ying A
authors.initials: YA
authors.lastname: Wang
authors.forename: Julius S
authors.initials: JS
authors.lastname: Ngwa
authors.forename: Roderick P
authors.initials: RP
authors.lastname: Martin
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Klein
authors.forename: Basma
authors.initials: B
authors.lastname: Hashmi
authors.forename: Yin
authors.initials: Y
authors.lastname: Ge
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Stanley Y
authors.initials: SY
authors.lastname: Shaw
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D012907:Smoking / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C412477:RERE protein, human; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase