@article {1251, title = {Association of coagulation-related and inflammation-related genes and factor VIIc levels with stroke: the Cardiovascular Health Study.}, journal = {J Thromb Haemost}, volume = {9}, year = {2011}, month = {2011 Feb}, pages = {267-74}, abstract = {

BACKGROUND: Thrombosis and inflammation are critical in stroke etiology, but associations of coagulation and inflammation gene variants with stroke, and particularly factor VII levels, are inconclusive.

OBJECTIVES: To test the associations between 736 single-nucleotide polymorphisms (SNPs) between tagging haplotype patterns of 130 coagulation and inflammation genes, and stroke events, in the 5888 participants aged >= 65 years of the observational Cardiovascular Health Study cohort.

PATIENTS/METHODS: With 16 years of follow-up, age-adjusted and sex-adjusted Cox models were used to estimate associations of SNPs and FVIIc levels with future stroke.

RESULTS: Eight hundred and fifteen strokes occurred in 5255 genotyped participants without baseline stroke (748 ischemic strokes; 586 among whites). Among whites, six SNPs were associated with stroke, with a nominal P-value of < 0.01: rs6046 and rs3093261 (F7); rs4918851 and rs3781387 (HABP2); and rs3138055 (NFKB1A) and rs4648004 (NFKB1). Two of these SNPs were associated with FVIIc levels (units of percentage activity): rs6046 (β = -18.5, P = 2.38 {\texttimes} 10(-83)) and rs3093261 (β = 2.99, P = 3.93 {\texttimes} 10(-6)). After adjustment for age, sex, race, and cardiovascular risk factors, the association of FVIIc quintiles (Q) with stroke were as follows (hazard ratio; 95\% confidence interval): Q1, reference; Q2, 1.4, 1.1-1.9); Q3, 1.1, 0.8-1.5); Q4, 1.5, 1.1-2.0); and Q5, 1.6, 1.2-2.2). Associations between SNPs and stroke were independent of FVIIc levels.

CONCLUSIONS: Variations in FVII-related genes and FVIIc levels were associated with risk of incident ischemic stroke in this elderly cohort, suggesting a potential causal role for FVII in stroke etiology.

}, keywords = {Blood Coagulation Factors, Cardiovascular Diseases, Cohort Studies, Factor VII, Female, Humans, Inflammation, Male, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Stroke}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2010.04149.x}, author = {Zakai, N A and Lange, L and Longstreth, W T and O{\textquoteright}Meara, E S and Kelley, J L and Fornage, M and Nikerson, D and Cushman, M and Reiner, A P} }