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Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.
Tuesday,2018-01-16 18:28 America/Los_Angeles — ecterry
| Title | Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Olson, NC, Raffield, LM, Lange, LA, Lange, EM, Longstreth, WT, Chauhan, G, Debette, S, Seshadri, S, Reiner, AP, Tracy, RP |
| Journal | J Thromb Haemost |
| Volume | 16 |
| Issue | 1 |
| Pagination | 19-30 |
| Date Published | 2018 Jan |
| ISSN | 1538-7836 |
| Abstract | <p><b>ESSENTIALS: </b>Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk.</p><p><b>SUMMARY: </b>Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). Objective Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke and mortality. Patients/Methods We measured FVIIa and FVIIa-AT in 3486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n = 2410) and examined associations of FVII phenotypes with incident cardiovascular disease. Results In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa, β = -25.9 mU mL-1 per minor allele; FVIIa-AT, β = -26.6 pm per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa, β = 7.8 mU mL-1 per minor allele; FVIIa-AT, β = 9.9 per minor allele). Adjusted for risk factors, a one standard deviation higher FVIIa was associated with increased risk of ischemic stroke (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all causes (HR, 1.08; 95% CI, 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR, 0.69; 95% CI, 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. Conclusions The results support the importance of the F7 and PROCR loci in variation in circulating FVIIa and FVIIa-AT. The findings suggest FVIIa is a risk factor for ischemic stroke in older adults, whereas higher FVIIa-AT may reflect mortality risk.</p> |
| DOI | 10.1111/jth.13899 |
| Alternate Journal | J. Thromb. Haemost. |
| PubMed ID | 29112333 |
| PubMed Central ID | PMC5760305 |
| Grant List | K99 HL129045 / HL / NHLBI NIH HHS / United States R01 HL071862 / HL / NHLBI NIH HHS / United States T32 HL129982 / HL / NHLBI NIH HHS / United States |
ePub date:
18/01