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PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study.
Tuesday,2012-11-06 12:10 America/Los_Angeles — eenright
| Title | PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study. |
| Publication Type | Journal Article |
| Year of Publication | 2008 |
| Authors | Reiner, AP, Carty, CL, Jenny, NS, Nievergelt, C, Cushman, M, Stearns-Kurosawa, DJ, Kurosawa, S, Kuller, LH, Lange, LA |
| Journal | J Thromb Haemost |
| Volume | 6 |
| Issue | 10 |
| Pagination | 1625-32 |
| Date Published | 2008 Oct |
| ISSN | 1538-7836 |
| Keywords | Aged, Aged, 80 and over, Aging, Antigens, CD, Blood Coagulation Factor Inhibitors, Cardiovascular Diseases, Coronary Disease, Endothelial Protein C Receptor, Female, Humans, Inflammation, Male, Middle Aged, Mortality, Polymorphism, Genetic, Protein C, Protein S, Receptors, Cell Surface, Risk, Stroke, Thrombosis |
| Abstract | <p><b>BACKGROUND AND OBJECTIVES: </b>Genes encoding protein C anticoagulant pathways are candidates for atherothrombotic and other aging-related disorders.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1111/j.1538-7836.2008.03118.x |
| Alternate Journal | J Thromb Haemost |
| PubMed ID | 18680534 |
| PubMed Central ID | PMC2856703 |
| Grant List | R01 HL071862-05A1 / HL / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States U01-HL66682 / HL / NHLBI NIH HHS / United States N01HV48195 / HL / NHLBI NIH HHS / United States N01HG65403 / HG / NHGRI NIH HHS / United States N01-HV-48195 / HV / NHLBI NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U19 AG023122 / AG / NIA NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States U01-HL080295 / HL / NHLBI NIH HHS / United States K08 HL080293-05 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC085083 / HC / NHLBI NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States R01-HL-071862 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U19 AG023122-05 / AG / NIA NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States N01 HC055222 / HC / NHLBI NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States R01 HL071862 / HL / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States K08 HL080293 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States U19-AG023122 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States U01 HL066682 / HL / NHLBI NIH HHS / United States |