Osteopontin gene variation and cardio/cerebrovascular disease phenotypes.
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.
Schmidt-Petersen
Klaus
K
Leibniz-Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Muenster, Domagkstrasse 3, Muenster, Germany.
Brand
Eva
E
Telgmann
Ralph
R
Nicaud
Viviane
V
Hagedorn
Claudia
C
Labreuche
Julien
J
Dördelmann
Corinna
C
Elbaz
Alexis
A
Gautier-Bertrand
Marion
M
Fischer
Jens W
JW
Evans
Alun
A
Morrison
Caroline
C
Arveiler
Dominique
D
Stoll
Monika
M
Amarenco
Pierre
P
Cambien
François
F
Paul
Martin
M
Brand-Herrmann
Stefan-Martin
SM
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
D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D053495:Osteopontin