TY - JOUR T1 - PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study. JF - J Thromb Haemost Y1 - 2008 A1 - Reiner, A P A1 - Carty, C L A1 - Jenny, N S A1 - Nievergelt, C A1 - Cushman, M A1 - Stearns-Kurosawa, D J A1 - Kurosawa, S A1 - Kuller, L H A1 - Lange, L A KW - Aged KW - Aged, 80 and over KW - Aging KW - Antigens, CD KW - Blood Coagulation Factor Inhibitors KW - Cardiovascular Diseases KW - Coronary Disease KW - Endothelial Protein C Receptor KW - Female KW - Humans KW - Inflammation KW - Male KW - Middle Aged KW - Mortality KW - Polymorphism, Genetic KW - Protein C KW - Protein S KW - Receptors, Cell Surface KW - Risk KW - Stroke KW - Thrombosis AB -

BACKGROUND AND OBJECTIVES: Genes encoding protein C anticoagulant pathways are candidates for atherothrombotic and other aging-related disorders.

METHODS: Using a tagSNP approach, and data from the Cardiovascular Health Study (CHS), we assessed associations of common polymorphisms of PROC, PROS1 and PROCR with: (i) plasma protein C, soluble protein C endothelial receptor (sEPCR) and protein S levels measured in a subsample of 336 participants at study entry; and (ii) risk of incident clinical outcomes [coronary heart disease (CHD), stroke, and mortality] in 4547 participants during follow-up. Secondarily, we explored associations between plasma protein C, protein S and sEPCR levels and other candidate genes involved in thrombosis, inflammation, and aging.

RESULTS: The PROCR Ser219Gly polymorphism (rs867186) was strongly associated with higher sEPCR levels, explaining 75% of the phenotypic variation. The PROCR Ser219Gly variant was also associated with higher levels of circulating protein C antigen. An IL10 polymorphism was associated with higher free protein S levels. The minor alleles of PROC rs2069901 and PROS1 rs4857343 were weakly associated with lower protein C and free protein S levels, respectively. There was no association between PROCR Ser219Gly and risk of CHD, stroke, or mortality. The minor allele of another common PROCR tagSNP, rs2069948, was associated with lymphoid PROCR mRNA expression and with increased risk of incident stroke and all-cause mortality, and decreased healthy survival during follow-up.

CONCLUSIONS: A common PROCR variant may be associated with decreased healthy survival in older adults. Additional studies are warranted to establish the role of PROCR variants in ischemic and aging-related disorders.

VL - 6 IS - 10 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18680534?dopt=Abstract ER -