Research article

Failure to replicate an association of SNPs in the oxidized LDL receptor gene (OLR1) with CAD

Joshua W Knowles^{* 1} , Themistocles L Assimes^{* 1} , Eric Boerwinkle⁷ , Stephen P Fortmann⁶ , Alan Go⁵ , Megan L Grove⁷ , Mark Hlatky^1,2 , Carlos Iribarren⁵ , Jun Li³ , Richard Myers³ , Neil Risch^4,5,8 , Stephen Sidney⁵ , Audrey Southwick³ , Kelly A Volcik⁷ and Thomas Quertermous¹

¹Division of Cardiovascular Medicine, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, CA, 94305-5406, USA

²Department of Health Research and Policy, Redwood Building, Stanford University School of Medicine, Stanford, CA 94305, USA

³Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, 975 California Ave, Palo Alto, CA, 94304, USA

⁴Institute for Human Genetics, University of California San Francisco, San Francisco, 94143, USA

⁵Division of Research, Kaiser Permanente of Northern California, Oakland, CA, 94612, USA

⁶Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA 94305-5705, USA

⁷Human Genetics Center, University of Texas Houston Health Science Center, 1200 Herman Pressler Dr., Houston, TX, 77030, USA

⁸Departments of Epidemiology, Biostatistics and Medicine, University of California, San Francisco, USA

author email corresponding author email* Contributed equally

BMC Medical Genetics 2008, 9:23doi:10.1186/1471-2350-9-23

Published:	2 April 2008

Abstract

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.

Conclusion

Our results do not support the presence of an association between selected common SNPs in OLR1 and the risk of clinical CAD.