Abstract
BackgroundThe 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.MethodsADVANCE 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.ResultsIn 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.ConclusionOur results do not support the presence of an association between selected common SNPs in OLR1 and the risk of clinical CAD.
Highlights
The lectin-like oxidized LDL receptor LOX-1 is believed to play a key role in atherogenesis and some reports suggest an association of OLR1 polymorphisms with myocardial infarction (MI)
Cases consisted subjects presenting with clinically significant CAD at a young age (< 45 years for males, < 55 years for females) or subjects presenting with incident stable angina or incident acute myocardial infarction (AMI) at an older age
Controls consisted of young subjects with no history of CAD including a subset of 479 subjects from the Coronary Artery Risk Development in Young Adults (CARDIA) Study [32], or subjects aged 60 to 72 with no history of CAD, cerebrovascular accident (CVA), or peripheral arterial disease (PAD)
Summary
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). Oxidized LDL (oxLDL) is thought to play a crucial role in the initiation of atherosclerotic lesions. The lectin-like oxidized LDL receptor (LOX-1) is expressed on endothelial cells, macrophages and vascular smooth muscle cells and binds and internalizes oxLDL leading to pleotropic effects on endothelial dysfunction and atherosclerosis. The human gene spans six exons and encodes a protein of 273 amino acids with four distinct domains: an N-terminal cytoplasmic domain crucial for cell sorting, a transmembrane domain, a neck domain with homology to the myosin heavy chain, and a C-terminal lectin-like domain (CTLD) which is responsible for binding oxLDL [2,3,4,5] (Figure 1). LOX-1 is found at high concentrations in human atherosclerotic lesions and overexpression of LOX-1 in apolipoprotein E -/- mice results in increased cholesterol deposition in coronary arteries [11,12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
