Failure to replicate an association of SNPs in the oxidized LDL receptor gene (OLR1) with CAD.
BACKGROUND
The lectin-like oxidized LDL receptor LOX-1 (encoded by OLR1) is believed to play a key role in atherogenesis and some reports suggest an association of OLR1 polymorphisms with myocardial infarction (MI). We tested whether single nucleotide polymorphisms (SNPs) in OLR1 are associated with clinically significant CAD in the Atherosclerotic Disease, VAscular FuNction, & Geneti C Epidemiology (ADVANCE) study.


METHODS
ADVANCE is a population-based case-control study of subjects receiving care within Kaiser Permanente of Northern California including a subset of participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We first resequenced the promoter, exonic, and splice site regions of OLR1 and then genotyped four single nucleotide polymorphisms (SNPs), including a non-synonymous SNP (rs11053646, Lys167Asn) as well as an intronic SNP (rs3736232) previously associated with CAD.


RESULTS
In 1,809 cases with clinical CAD and 1,734 controls, the minor allele of the coding SNP was nominally associated with a lower odds ratio (OR) of CAD across all ethnic groups studied (minimally adjusted OR 0.8, P = 0.007; fully adjusted OR 0.8, P = 0.01). The intronic SNP was nominally associated with an increased risk of CAD (minimally adjusted OR 1.12, p = 0.03; fully adjusted OR 1.13, P = 0.03). However, these associations were not replicated in over 13,200 individuals (including 1,470 cases) in the Atherosclerosis Risk in Communities (ARIC) study.


CONCLUSIONS
Our results do not support the presence of an association between selected common SNPs in OLR1 and the risk of clinical CAD.
Knowles
Joshua W
JW
Division of Cardiovascular Medicine, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, CA 94305-5406, USA. knowlej@stanford.edu
Assimes
Themistocles L
TL
Boerwinkle
Eric
E
Fortmann
Stephen P
SP
Go
Alan
A
Grove
Megan L
ML
Hlatky
Mark
M
Iribarren
Carlos
C
Li
Jun
J
Myers
Richard
R
Risch
Neil
N
Sidney
Stephen
S
Southwick
Audrey
A
Volcik
Kelly A
KA
Quertermous
Thomas
T
D000328:Adult; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D051127:Scavenger Receptors, Class E / Q000235:genetics*
C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E