title: Osteopontin gene variation and cardio/cerebrovascular disease phenotypes.
abstract: We aimed at associating common osteopontin (OPN) gene variants with cardiovascular disease phenotypes.We scanned the OPN gene in 190 chromosomes from myocardial infarction (MI) patients and identified five variants in the promoter, three synonymous and one non-synonymous variant. All variants were investigated in case-control studies for MI (ECTIM: 990 cases, 900 controls) and brain infarction (BI) (GENIC: 466 cases, 444 controls). Promoter variants were functionally analyzed by bandshift assays, the coding D147D [T/C] by Western blot. Allele D147D C was independently and significantly associated with lower apoB levels (P=0.044 [ECTIM] P=0.03 [GENIC]), its allele frequency was significantly lower in patients with BI compared to controls (OR [95% CI] 0.39 [0.20-0.74], P=0.004), and C allele carriers had a significantly lower frequency of presence of carotid plaques (P=0.02). Bandshifts with HepG2 and Ea.hy926 nuclear proteins did not reveal any functionality of promoter variants, whereas the OPN-441C-containing construct resulted in reduced OPN protein expression in Western blots, complying with its potential protective effect on the phenotypes studied.We here provide evidence that a portion of the OPN locus is likely to associate with cardiovascular disease-related phenotypes. However, further experiments are warranted to clarify the functional role of OPN variants.
authors.affiliation: Leibniz-Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Muenster, Domagkstrasse 3, Muenster, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmidt-Petersen
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
authors.forename: Ralph
authors.initials: R
authors.lastname: Telgmann
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Claudia
authors.initials: C
authors.lastname: Hagedorn
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.forename: Corinna
authors.initials: C
authors.lastname: Dördelmann
authors.forename: Alexis
authors.initials: A
authors.lastname: Elbaz
authors.forename: Marion
authors.initials: M
authors.lastname: Gautier-Bertrand
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Alun
authors.initials: A
authors.lastname: Evans
authors.forename: Caroline
authors.initials: C
authors.lastname: Morrison
authors.forename: Dominique
authors.initials: D
authors.lastname: Arveiler
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand-Herrmann
mesh_terms: D000368:Aged; D020520:Brain Infarction / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002561:Cerebrovascular Disorders / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D053495:Osteopontin / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D014463:Ultrasonography
chemical_list: D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D053495:Osteopontin