The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke
Anna Helgadottir,Andrei Manolescu,Gudmar Thorleifsson,Solveig Gretarsdottir,Helga Jonsdottir,Unnur Thorsteinsdottir,Nilesh J. Samani,Gudmundur Gudmundsson,Struan F.A. Grant,Gudmundur Thorgeirsson,Sigurlaug Sveinbjörnsdóttir,Einar M. Valdimarsson,Stefan E Matthiasson,Halldor Johannsson,Olof Gudmundsdottir,Mark E. Gurney,Jesus Sainz,Margret Thorhallsdottir,Margret B. Andresdottir,Michael L. Frigge,Eric J. Topol,Augustine Kong,Vilmundur Gudnason,Hakon Hakonarson,Jeffrey R. Gulcher,Kari Stefansson +25 more
Reads0
Chats0
TLDR
It is concluded that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall.Abstract:
We mapped a gene predisposing to myocardial infarction to a locus on chromosome 13q12-13. A four-marker single-nucleotide polymorphism (SNP) haplotype in this locus spanning the gene ALOX5AP encoding 5-lipoxygenase activating protein (FLAP) is associated with a two times greater risk of myocardial infarction in Iceland. This haplotype also confers almost two times greater risk of stroke. Another ALOX5AP haplotype is associated with myocardial infarction in individuals from the UK. Stimulated neutrophils from individuals with myocardial infarction produce more leukotriene B4, a key product in the 5-lipoxygenase pathway, than do neutrophils from controls, and this difference is largely attributed to cells from males who carry the at-risk haplotype. We conclude that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall.read more
Citations
More filters
Journal ArticleDOI
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Mark I. McCarthy,Willem H. Ouwehand,Nilesh J. Samani,John A. Todd,Peter Donnelly,Jeffrey C. Barrett,Dan Davison,Doug Easton,David M. Evans,H. T. Leung,Jonathan Marchini,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,James P. Boorman,Barbara Cant,Ursula Everson,Judith M. Hussey,Jennifer Jolley,Alexandra S. Knight,Kerstin Koch,Elizabeth Meech,Sarah Nutland,Christopher Prowse,Helen Stevens,Niall C. Taylor,Graham R. Walters,Neil Walker,Nicholas A. Watkins,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katherine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskvina,Ivan Nikolov,Michael Conlon O'Donovan,Michael John Owen,David A. Collier,Amanda Elkin,Anne Farmer,Richard Williamson,Peter McGuffin,Allan H. Young,I. Nicol Ferrier,Stephen G. Ball,Anthony J. Balmforth,Jennifer H. Barrett,D. Timothy Bishop,Mark M. Iles,Azhar Maqbool,Nadira Yuldasheva,Alistair S. Hall,Peter S. Braund,Richard J. Dixon,Massimo Mangino,Suzanne Stevens,John R. Thompson,Francesca Bredin,Mark Tremelling,Miles Parkes,Hazel E. Drummond,Charlie W. Lees,Elaine R. Nimmo,Jack Satsangi,Sheila A. Fisher,Alastair Forbes,Cathryn M. Lewis,Clive M. Onnie,Natalie J. Prescott,Jeremy D. Sanderson,Christopher G. Mathew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,G. Mark Lathrop,John M. C. Connell,Anna F. Dominiczak,Carolina A. Braga Marcano,Beverley Burke,Richard Dobson,Johannie Gungadoo,Kate L. Lee,Patricia B. Munroe,Stephen Newhouse,Abiodun Onipinla,Chris Wallace,Mingzhan Xue,Mark J. Caulfield,Martin Farrall,Anne Barton,Ian N. Bruce,Hannah Donovan,Steve Eyre,Paul D. Gilbert,Samantha L. Hider,Anne Hinks,Sally John,Catherine Potter,Alan J. Silman,Deborah P M Symmons,Wendy Thomson,Jane Worthington,David B. Dunger,Barry Widmer,Timothy M. Frayling,Rachel M. Freathy,Hana Lango,John R. B. Perry,Beverley M. Shields,Michael N. Weedon,Andrew T. Hattersley,Graham A. Hitman,Mark Walker,Kate S. Elliott,Christopher J. Groves,Cecilia M. Lindgren,Nigel W. Rayner,Nicholas J. Timpson,Eleftheria Zeggini,Melanie J. Newport,Giorgio Sirugo,Emily J. Lyons,Fredrik O. Vannberg,Adrian V. S. Hill,Linda A. Bradbury,C Farrar,J J Pointon,Paul Wordsworth,Matthew A. Brown,Jayne A. Franklyn,Joanne M. Heward,Matthew J. Simmonds,Stephen C. L. Gough,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Maria Ban,An Goris,Stephen Sawcer,Alastair Compston,David J. Conway,Muminatou Jallow,Kirk A. Rockett,Suzannah Bumpstead,Amy Chaney,Kate Downes,Mohammed J. R. Ghori,Rhian Gwilliam,Sarah E. Hunt,Michael Inouye,Andrew Keniry,Emma King,Ralph McGinnis,Simon C. Potter,Rathi Ravindrarajah,Pamela Whittaker,Claire Widden,David Withers,Niall Cardin,Teresa Ferreira,Joanne Pereira-Gale,Ingileif B. Hallgrímsdóttir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,A Compston +195 more
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI
The immune system in atherosclerosis.
TL;DR: Innate as well as adaptive immune responses have been identified in atherosclerosis, with components of cholesterol-carrying low-density lipoprotein triggering inflammation, T cell activation and antibody production during the course of disease.
Journal ArticleDOI
Cytokines in atherosclerosis: pathogenic and regulatory pathways.
Alain Tedgui,Ziad Mallat +1 more
TL;DR: Based on the current knowledge of the role of cytokines in atherosclerosis, some novel therapeutic strategies to combat this disease are proposed and the potential of circulating cytokine levels as biomarkers of coronary artery disease is discussed.
Journal ArticleDOI
Primary Prevention of Ischemic Stroke A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.
Larry B. Goldstein,Robert J. Adams,Mark J. Alberts,Lawrence J. Appel,Lawrence M. Brass,Cheryl Bushnell,Antonio Culebras,Thomas J. DeGraba,Philip B. Gorelick,John R. Guyton,Robert G. Hart,George Howard,Margaret Kelly-Hayes,J.V. (Ian) Nixon,Ralph L. Sacco +14 more
TL;DR: In this paper, the authors provide an overview of the evidence on various established and potential stroke risk factors and provide recommendations for the reduction of stroke risk, and when appropriate, formulate recommendations based on standard American Heart Association criteria.
Journal ArticleDOI
Biomarkers of cardiovascular disease: molecular basis and practical considerations.
TL;DR: This review provides an overview of the molecular basis of biomarker discovery and selection and the practical considerations that are a prerequisite to their clinical use.
References
More filters
Journal ArticleDOI
Maximum likelihood from incomplete data via the EM algorithm
Journal ArticleDOI
Inflammation in atherosclerosis
TL;DR: The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.
Journal ArticleDOI
Coronary Plaque Disruption
TL;DR: This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.
Journal Article
Parametric and nonparametric linkage analysis: a unified multipoint approach.
TL;DR: It is shown that NPL is robust to uncertainty about mode of inheritance, is much more powerful than commonly used nonparametric methods, and loses little power relative to parametric linkage analysis, and appears to be the method of choice for pedigree studies of complex traits.
Journal Article
Atherosclerosis : Vascular biology
TL;DR: It is now clear that atherosclerosis is not simply an inevitable degenerative consequence of ageing, but rather a chronic inflammatory condition that can be converted into an acute clinical event by plaque rupture and thrombosis.
Related Papers (5)
Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.
Anna Helgadottir,Andrei Manolescu,Agnar Helgason,Gudmar Thorleifsson,Unnur Thorsteinsdottir,Daniel F. Gudbjartsson,Solveig Gretarsdottir,Kristinn P. Magnusson,Gudmundur Gudmundsson,Andrew A. Hicks,Thorlakur Jonsson,Struan F.A. Grant,Jesus Sainz,Stephen J. O'Brien,Sigurlaug Sveinbjörnsdóttir,Einar M. Valdimarsson,Stefan E Matthiasson,Allan I. Levey,Jerome L. Abramson,Murdach P Reilly,Viola Vaccarino,Megan L. Wolfe,Vilmundur Gudnason,Arshed A. Quyyumi,Eric J. Topol,Daniel J. Rader,Gudmundur Thorgeirsson,Jeffrey R. Gulcher,Hakon Hakonarson,Augustine Kong,Kari Stefansson +30 more
The gene encoding phosphodiesterase 4D confers risk of ischemic stroke.
Solveig Gretarsdottir,Gudmar Thorleifsson,Sigridur Th. Reynisdottir,Andrei Manolescu,Sif Jonsdottir,Thorbjorg Jonsdottir,Thorunn Gudmundsdottir,Sigrun M. Bjarnadottir,Olafur B. Einarsson,Herdis M. Gudjonsdottir,Malcolm Hawkins,Gudmundur Gudmundsson,Hrefna Gudmundsdottir,Hjalti Andrason,Asta Solilja Gudmundsdottir,Matthildur Sigurdardottir,Thomas T. Chou,Joseph Nahmias,Shyamali Goss,Sigurlaug Sveinbjörnsdóttir,Einar M. Valdimarsson,Finnbogi Jakobsson,Uggi Agnarsson,Vilmundur Gudnason,Gudmundur Thorgeirsson,Jürgen Fingerle,Mark E. Gurney,Daniel F. Gudbjartsson,Michael L. Frigge,Augustine Kong,Kari Stefansson,Jeffrey R. Gulcher +31 more