Association of the novel single-nucleotide polymorphism which increases oxidized low-density lipoprotein levels with cerebrovascular disease events

Kari-Matti Mäkelä; Matthew Traylor; Niku Oksala; Marcus E Kleber; Ilkka Seppälä; Leo-Pekka Lyytikäinen; Jussi A Hernesniemi; Mika Kähönen; Steve Bevan; Peter M Rothwell; Cathie Sudlow; Martin Dichgans; Wellcome Trust Case Control Consortium 2 (WTCCC2); Graciela Delgado; Tanja B Grammer; Hubert Scharnagl; Hugh S Markus; Winfried März; Terho Lehtimäki

doi:10.1016/j.atherosclerosis.2014.03.002

Association of the novel single-nucleotide polymorphism which increases oxidized low-density lipoprotein levels with cerebrovascular disease events

Atherosclerosis. 2014 May;234(1):214-7. doi: 10.1016/j.atherosclerosis.2014.03.002. Epub 2014 Mar 14.

Authors

Kari-Matti Mäkelä¹, Matthew Traylor², Niku Oksala³, Marcus E Kleber⁴, Ilkka Seppälä⁵, Leo-Pekka Lyytikäinen⁵, Jussi A Hernesniemi⁶, Mika Kähönen⁷, Steve Bevan⁸, Peter M Rothwell⁹, Cathie Sudlow¹⁰, Martin Dichgans¹¹; Wellcome Trust Case Control Consortium 2 (WTCCC2); Graciela Delgado⁴, Tanja B Grammer⁴, Hubert Scharnagl¹², Hugh S Markus⁸, Winfried März¹³, Terho Lehtimäki⁵

Affiliations

¹ School of Medicine, University of Tampere, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland. Electronic address: kari-matti.makela@uta.fi.
² Stroke and Dementia Research Centre, St George's University of London, London, United Kingdom.
³ School of Medicine, University of Tampere, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland.
⁴ Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Germany.
⁵ School of Medicine, University of Tampere, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
⁶ School of Medicine, University of Tampere, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Internal Medicine, North Karelia Central Hospital, Joensuu, Finland.
⁷ Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Tampere, Finland.
⁸ Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁹ Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
¹⁰ Division of Clinical Neurosciences and Insititute of Genetics and Molecular Medicine, University of Edinburgh, UK.
¹¹ Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹² Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Graz, Graz, Austria.
¹³ Synlab Services GmbH, Mannheim, Germany; Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Graz, Graz, Austria.

PMID: 24681816
DOI: 10.1016/j.atherosclerosis.2014.03.002

Abstract

Background and purpose: Patients with genetic background for high circulating oxidized low-density lipoprotein (oxLDL) levels might be at an increased risk of cerebrovascular disease (CVD).

Methods: The association of oxLDL-variant rs676210 with CVD events was studied in patients undergoing coronary angiography (study A; N = 2913 [271 cases]). We sought to replicate the results in a large genome-wide association study meta-analysis of ischaemic stroke (study B; N = 3548 cases, 5972 controls).

Results: In study A, the prevalence of hypertension, diabetes and >50% carotid stenosis as well as the levels of LDL cholesterol differed significantly between cases and controls. In a logistic regression model adjusted for the significant covariates, rs676210 associated with CVD events (p = 0.030; odds ratio = 1.29 [95% confidence interval 1.03‒1.63] for risk allele G). In study B, rs676210 did not associate with the history of ischaemic stroke.

Conclusions: The oxLDL levels increasing variant rs676210 associates with CVD events in patients undergoing coronary angiography.

Keywords: Genetics; Oxidized low-density lipoprotein; Single nucleotide polymorphism; Stroke; Transient ischaemic attack.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain Ischemia / blood
Brain Ischemia / complications
Brain Ischemia / genetics
Cerebrovascular Disorders / blood*
Cerebrovascular Disorders / genetics*
Female
Humans
Lipoproteins, LDL / blood*
Lipoproteins, LDL / genetics
Male
Polymorphism, Single Nucleotide*
Stroke / blood
Stroke / etiology
Stroke / genetics

Substances

Lipoproteins, LDL
oxidized low density lipoprotein

Abstract

Publication types

MeSH terms

Substances

Grants and funding