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Disparate Associations Of A Functional Promoter Polymorphism In Pck1 With Carotid Wall Ultrasound Traits, Robert A. Hegele, Khalid Z. Al-Shali, Andrew A. House, Anthony J.G. Hanley, Stewart B. Harris, Mary Mamakeesick, Aaron Fenster, Bernard Zinman, Henian Cao, J. David Spence
Disparate Associations Of A Functional Promoter Polymorphism In Pck1 With Carotid Wall Ultrasound Traits, Robert A. Hegele, Khalid Z. Al-Shali, Andrew A. House, Anthony J.G. Hanley, Stewart B. Harris, Mary Mamakeesick, Aaron Fenster, Bernard Zinman, Henian Cao, J. David Spence
Department of Medicine Publications
Background and Purpose - Cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32), encoded by PCK1, catalyzes the first committed step in gluconeogenesis. We previously showed that a -232C>G promoter polymorphism within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription results in loss of negative regulation by insulin, contributing to worsened metabolic control in the context of insulin resistance. We hypothesized that this polymorphism would be associated with carotid atherosclerosis in a sample of 150 aboriginal Canadians. Methods - Dependent variables were 2 distinct carotid traits, namely intima-media thickness (IMT) assessed using B-mode ultrasound and total carotid plaque volume …
Noninvasive Phenotypes Of Atherosclerosis: Similar Windows But Different Views, J. David Spence, Robert A. Hegele
Noninvasive Phenotypes Of Atherosclerosis: Similar Windows But Different Views, J. David Spence, Robert A. Hegele
Department of Medicine Publications
Background and Purpose-Noninvasive measures of atherosclerosis, such as carotid intima-media thickness, total carotid plaque area, and carotid stenosis, probably represent different phenotypes with distinct determinants. For instance, total carotid plaque area may reflect atherosclerotic lesion size more closely than carotid stenosis, which instead may reflect hemodynamic compromise within the arterial lumen. Methods-In 1821 patients from a Premature Atherosclerosis Clinic, we studied determinants of total carotid plaque area and carotid stenosis as measured by ultrasound using multivariate regression analysis with traditional risk factors and some emerging risk factors. Results-Regression modeling showed that (1) traditional atherosclerosis risk factors were more strongly associated …
Lipoprotein Lipase (Lpl) Gene Variation And Progression Of Carotid Artery Plaque, J. David Spence, Matthew R. Ban, Robert A. Hegele
Lipoprotein Lipase (Lpl) Gene Variation And Progression Of Carotid Artery Plaque, J. David Spence, Matthew R. Ban, Robert A. Hegele
Department of Medicine Publications
Background and Purpose - Coding single nucleotide polymorphisms (cSNPs) in the lipoprotein lipase (LPL) gene have been associated with lipoprotein phenotypes and vascular disease risk. We studied the association between LPL cSNPs and a novel noninvasive measure of disease, namely, cross-sectional carotid plaque area (CPA) on B-mode ultrasound. Methods - Four hundred fifty-two patients from an atherosclerosis prevention clinic had determinations of baseline and total CPA. Traditional atherosclerosis risk factors were recorded, and the LPL D9N, N291S, and S447X cSNPs were genotyped. Multiple regression analysis was used to identify determinants of CPA. Results - Minor allele frequencies for LPL D9N, …
Plasma Homocyst(E)Ine Concentration, But Not Mthfr Genotype, Is Associated With Variation In Carotid Plaque Area, J. David Spence, M. Rene Malinow, Peter A. Barnett, Ali J. Marian, David Freeman, Robert A. Hegele
Plasma Homocyst(E)Ine Concentration, But Not Mthfr Genotype, Is Associated With Variation In Carotid Plaque Area, J. David Spence, M. Rene Malinow, Peter A. Barnett, Ali J. Marian, David Freeman, Robert A. Hegele
Department of Medicine Publications
Background and Purpose - Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis. A common cause of elevated plasma H(e) concentration is a thermolabile mutation (677T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR). We sought to determine whether plasma H(e) concentration or MTHFR genotype would be more strongly associated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis. Methods - In 307 subjects who were ascertained through a premature atherosclerosis clinic, we measured CPA with 2- dimensional ultrasound and also determined traditional atherosclerosis risk factors, in addition to plasma H(e) concentration and MTHFR genotypes. Results - We …