Single nucleotide polymorphism on chromosome 9p21 and endothelial progenitor cells in a general population cohort

Objective: Recent studies have revealed that sequence variation on chromosome 9p21 is a major genetic determinant for coronary heart disease and stroke, however, the underlying mechanism remains unknown. This genomic region contains the gene encoding cyclin-dependent kinase 2A, a regulator of proliferation and differentiation of endothelial progenitor cell (EPC) which has been implicated in vascular repair and protection against cardiovascular disease. We investigated whether carriers and non-carriers of the chromosome 9p21 variation differed in their number and function of EPCs. Methods: We genotyped a cohort of 769 individuals (who participated in the Bruneck Study) for the single nucleotide polymorphism rs1333049 on chromosome 9p21 and determined circulating EPC numbers and EPC colony formation units (n = 538 and 512, respectively). Results: There was no evidence of reduced EPC numbers or colony formation units in carriers of the chromosome 9p21 risk variant. On the contrary, circulating EPC numbers and colony formation units tended to be higher in carriers of the variant (p = 0.189 for EPC numbers and p = 0.190 for EPC colony formation units). Conclusion: These results indicate that the chromosome 9p21 variant does not influence the risk of coronary heart disease and stroke through an effect on circulating EPCs. (C) 2009 Elsevier Ireland Ltd. All rights reserved.