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 (r(2)>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.
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 (r(2)>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.
Authors: Richard Shen; Jian-Bing Fan; Derek Campbell; Weihua Chang; Jing Chen; Dennis Doucet; Jo Yeakley; Marina Bibikova; Eliza Wickham Garcia; Celeste McBride; Frank Steemers; Francisco Garcia; Bahram G Kermani; Kevin Gunderson; Arnold Oliphant Journal: Mutat Res Date: 2005-06-03 Impact factor: 2.433
Authors: Natalya V Narizhneva; Olga V Razorenova; Eugene A Podrez; Juhua Chen; Unni M Chandrasekharan; Paul E DiCorleto; Edward F Plow; Eric J Topol; Tatiana V Byzova Journal: FASEB J Date: 2005-04-15 Impact factor: 5.191
Authors: Susanna Moskau; Astrid Golla; Christoph Grothe; Monika Boes; Christoph Pohl; Thomas Klockgether Journal: Stroke Date: 2004-11-29 Impact factor: 7.914
Authors: Shyam Prabhakaran; Tatjana Rundek; Romel Ramas; Mitchell S V Elkind; Myunghee Cho Paik; Bernadette Boden-Albala; Ralph L Sacco Journal: Stroke Date: 2006-09-28 Impact factor: 7.914
Authors: Cláudia N Ferreira; Maria G Carvalho; Karina B Gomes; Helton J Reis; Ana-Paula Fernandes; András Palotás; Marinez O Sousa Journal: Exp Biol Med (Maywood) Date: 2014-07-29
Authors: Peter Kraft; Christiane Drechsler; Ignaz Gunreben; Bernhard Nieswandt; Guido Stoll; Peter Ulrich Heuschmann; Christoph Kleinschnitz Journal: PLoS One Date: 2014-06-17 Impact factor: 3.240