Association between Variations in Coagulation System Genes and Carotid Plaque

Autor: David Della-Morte, Ashley Beecham, Ralph L. Sacco, Mark S. McClendon, Susan H. Blanton, Tatjana Rundek, Hannah Gardener, Liyong Wang, Chuanhui Dong
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Carotid Artery Diseases
Male
Candidate gene
Pathology
medicine.medical_specialty
Linkage disequilibrium
Genome-wide association study
Single-nucleotide polymorphism
Comorbidity
Biology
Polymorphism
Single Nucleotide
Article
Thrombospondin 1
Risk Factors
Plasminogen Activator Inhibitor 1
von Willebrand Factor
medicine
Diabetes Mellitus
Prevalence
Humans
Genetic Predisposition to Disease
Prospective Studies
Age of Onset
Blood Coagulation
Genetic Association Studies
Subclinical infection
Aged
Dyslipidemias
Ultrasonography
Haplotype
Dominican Republic
Smoking
Epistasis
Genetic
Middle Aged
medicine.disease
Plaque
Atherosclerotic
Logistic Models
Neurology
Haplotypes
Immunology
Hypertension
SERPINE1 Gene
Female
New York City
Neurology (clinical)
Dyslipidemia
Follow-Up Studies
Genome-Wide Association Study
Popis: Objective Genetic variation in coagulation and fibrinolysis may affect the development of subclinical atherosclerosis modifying the risk of stroke and cardiovascular disease. However, data on the relationship between subclinical atherosclerosis and genes involved in the coagulation system are sparse. The objective of this study is to examine the association between single nucleotide polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque phenotypes. Methods From the Genetic Determinants of Subclinical Carotid Disease Study, 287 Dominicans were examined for carotid plaque presence, thickness, and surface irregularity by high-resolution B-mode carotid ultrasound. Logistic regression was used to test for association between 101 SNPs in 23 coagulation system genes and plaque phenotypes while controlling for age, sex, smoking, hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions between genes were examined. A follow-up of SNPs in moderate to high (r2 > 0.25) linkage disequilibrium (LD) with those implicated in the discovery analysis (p ≤ 0.01) was performed in an independent sample of 301 Dominicans. Results The prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean age (65 ± 8 discovery; 65 ± 9 follow-up) of the participants was similar in both datasets. Two genes (vWF and THBS1) were associated (p ≤ 0.01) with plaque size and surface irregularity. In follow-up, 5 SNPs in vWF were associated (p ≤ 0.05) with plaque size. SERPINE1 was an additional gene of interest in the haplotype and interaction analyses. Conclusions Variation in the vWF, THBS1, and SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic plaque.
Databáze: OpenAIRE
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