Published Online
on June 16, 2003

A more recent version of this article appeared on July 1, 2003

This Article Full Text (PDF) All Versions of this Article: 107/25/3146    most recent 01.CIR.0000074207.85796.36v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Q. Articles by Kamboh, M. I. Search for Related Content PubMed PubMed Citation Articles by Chen, Q. Articles by Kamboh, M. I. Related Collections Risk Factors Genetics of cardiovascular disease

Submitted on August 16, 2002
Revised on March 26, 2003
Accepted on March 31, 2003

Genetic Variation in Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 (LOX1) Gene and the Risk of Coronary Artery Disease

Qi Chen PhD, Steven E. Reis MD, Candace Kammerer PhD, Wendy Y. Craig PhD, Sue E. LaPierre BS, Erin Luedecking Zimmer PhD, Dennis M. McNamara MD, Daniel F. Pauly MD, PhD, Barry Sharaf MD, Richard Holubkov PhD, C. Noel Bairey Merz MD, George Sopko MD, Franklin Bontempo MD, and M. Ilyas Kamboh PhD^*

From the Department of Human Genetics (Q.C., C.K., E.L.Z., M.I.K.), Cardiovascular Institute (S.E.R., D.M.M.), and Department of Medicine (F.B.), University of Pittsburgh, Pittsburgh, Pa; Foundation for Blood Research, Scarborough, Maine (W.Y.C., S.E.L.); Division of Cardiology, University of Florida, Gainesville (D.F.P.); Division of Cardiology, Brown University, Providence, RI (B.S.); Department of Family and Preventive Medicine, University of Utah, Salt Lake City (R.H.); Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, Calif (C.N.B.M.); and the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (G.S.).

^* To whom correspondence should be addressed. E-mail: ilyas.kamboh{at}mail.hgen.pitt.edu.

Background--We examined the association of 3 polymorphisms in the lectin-like oxidized LDL receptor-1 (LOX1 or OLR1) gene with coronary artery disease in the Women's Ischemia Syndrome Evaluation (WISE) study population.

Methods and Results--The WISE sample comprised 589 white and 122 black women who underwent angiography for suspected ischemia. The sample was divided into 3 groups: <20% stenosis (38.7%), 20% to 49% stenosis (24.9%), and 50% stenosis (35.3%). The three LOX1 polymorphisms (intron 4/GA, intron 5/TG, and 3` UTR/TC) were in linkage disequilibrium and thus behaved as a single polymorphism. The frequency of the 3`UTR/T allele was significantly higher in whites than blacks (49% versus 19%; P<0.0001). Among white women, the frequency of the 3`UTR/T allele carriers (TC+TT genotypes) increased gradually from 67.9% to 75.0% and 79.2% in the <20%, 20% to 49%, and 50% stenosis groups, respectively (<sup>2</sup> trend=6.23; P=0.013). Logistic regression analyses indicated that APOE (odds ratio, 1.90; P=0.007) and LOX1 (odds ratio, 1.67; P=0.025) genotypes were independently associated with the risk of disease and that there was no interaction between the two genes. The 3`UTR/T allele carriers also had significantly higher IgG anti-oxLDL levels than individuals carrying the CC genotype (0.94±0.20 versus 0.86±0.16; P=0.032). Furthermore, our electrophoretic mobility shift assay data show that the 3`UTR polymorphic sequence affects the binding of a putative transcription factor in an allele-specific manner.

Conclusions--Our data suggest that common genetic variation in the LOX1 gene may be associated with the risk of coronary artery disease in white women.

Key words: risk factors • coronary disease • genetics

This article has been cited by other articles:

				A. Ghazalpour, X. Wang, A. J. Lusis, and M. Mehrabian Complex Inheritance of the 5-Lipoxygenase Locus Influencing Atherosclerosis in Mice Genetics, June 1, 2006; 173(2): 943 - 951. [Abstract] [Full Text] [PDF]

				H. Khatib, S. D. Leonard, V. Schutzkus, W. Luo, and Y. M. Chang Association of the OLR1 Gene with Milk Composition in Holstein Dairy Cattle J Dairy Sci, May 1, 2006; 89(5): 1753 - 1760. [Abstract] [Full Text] [PDF]

				A. A. Quyyumi Women and Ischemic Heart Disease: Pathophysiologic Implications From the Women's Ischemia Syndrome Evaluation (WISE) Study and Future Research Steps J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S66 - S71. [Abstract] [Full Text] [PDF]

				J. L. Mehta, J. Chen, P. L. Hermonat, F. Romeo, and G. Novelli Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): A critical player in the development of atherosclerosis and related disorders Cardiovasc Res, January 1, 2006; 69(1): 36 - 45. [Abstract] [Full Text] [PDF]

				K. Inoue, Y. Arai, H. Kurihara, T. Kita, and T. Sawamura Overexpression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Induces Intramyocardial Vasculopathy in Apolipoprotein E-Null Mice Circ. Res., July 22, 2005; 97(2): 176 - 184. [Abstract] [Full Text] [PDF]

				A. D'Introno, V. Solfrizzi, A. M. Colacicco, C. Capurso, F. Torres, S. A. Capurso, A. Capurso, and F. Panza Polymorphisms in the Oxidized Low-Density Lipoprotein Receptor-1 Gene and Risk of Alzheimer's Disease J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2005; 60(3): 280 - 284. [Abstract] [Full Text] [PDF]

				M. D. Badzioch, R. P. Igo Jr, F. Gagnon, J. D. Brunzell, R. M. Krauss, A. G. Motulsky, E. M. Wijsman, and G. P. Jarvik Low-Density Lipoprotein Particle Size Loci in Familial Combined Hyperlipidemia: Evidence for Multiple Loci From a Genome Scan Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1942 - 1950. [Abstract] [Full Text] [PDF]

				R Mango, F Clementi, P Borgiani, G B Forleo, M Federici, G Contino, E Giardina, L Garza, I E Fahdi, R Lauro, et al. Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction J. Med. Genet., December 1, 2003; 40(12): 933 - 936. [Full Text]