8th February 2008

Scientists reveal a new target to fight bad cholesterol

Genetic link to levels of LDLcholesterol


The strongest association signals (dark boxes) are localised to a 14-kb region of chromosome 1 that includes the 3'-untranslated region of the <em>CELSR2</em> gene.

Scientists have uncovered a new region in the genome that is responsible for the bodys ability to regulate bad cholesterol which is linked to heart attack and stroke. Their findings are published in the Lancet.

The researchers found three genetic variations in the same region on chromosome 1 which were all linked to levels of LDL-cholesterol in the blood.

Teams from the Medical Research Council Epidemiology Unit, the Wellcome Trust Sanger Institute, Cambridge University and GlaxoSmithKline, studied data from large numbers of people across Europe. They looked at genome-wide scans of more than eleven thousand people to find out which genes affect LDL-cholesterol levels.

" This region has been previously associated with coronary artery disease through the efforts of of the Wellcome Trust Case Control Consortium and Cardiogenics but the findings of this study push our understanding further revealing its implication in lipid levels "

Dr Panos Deloukas

Dr Manjinder Sandhu, from the MRC Epidemiology Unit and Department of Public Health & Primary Care, Cambridge University, and lead researcher for the study said: "While therapies exist to lower cholesterol levels in people whose levels are too high, much is still unknown about the mechanisms that underlie cholesterol regulation and why some people seem to produce more than others."

He went on: "Although what you eat is definitely a factor in your cholesterol levels and some bad cholesterol is dietary in origin, the majority of LDL-cholesterol is produced by the body. Performing a genome-wide study, looking for areas which are associated with cholesterol levels helps us to find out why some people produce more than others."

"We might be able to use this information to identify which people are particularly at risk of developing cholesterol problems. We can also look at the function of the genes involved and find out in what way someone may be having problems regulating bad cholesterol levels. This could help us to design more specific and appropriate treatments," said Dr Sandhu.

Professor Nick Wareham, director of the MRC Epidemiology Unit explained the scale of the study: "This represents a mammoth statistical effort by teams in publicly-funded research establishments, the charitable sector and industry."

"The collaborative spirit in which the research was carried out and the access to the data and expertise of academic and industry scientists has made this a particularly exciting project, generating solid data that provides novel insights into the regulation of cholesterol."

Professor Paul Matthews, Vice-president of Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, emphasised the importance of a new partnership in genetics research between GSK and the MRC to find causes for common diseases:

"GSK is looking for innovation to bring better medicines to patients. Breakthroughs when dealing with big clinical problems can only come out of open, highly collaborative science like this. GSK is committed to this partnership which it is hoped will yield further results."

Dr Panos Deloukas, Senior Investigator at the Wellcome Trust Sanger Institute, where part of the study was carried out, emphasized the need for large-scale research that can be enabled through pooled analysis of data sets.

"This region has been previously associated with coronary artery disease through the efforts of of the Wellcome Trust Case Control Consortium and Cardiogenics but the findings of this study push our understanding further revealing its implication in lipid levels."

Notes to Editors

Publication details

  • LDL-cholesterol concentrations: a genome-wide association study.

    Sandhu MS, Waterworth DM, Debenham SL, Wheeler E, Papadakis K, Zhao JH, Song K, Yuan X, Johnson T, Ashford S, Inouye M, Luben R, Sims M, Hadley D, McArdle W, Barter P, Kesäniemi YA, Mahley RW, McPherson R, Grundy SM, Wellcome Trust Case Control Consortium, Bingham SA, Khaw KT, Loos RJ, Waeber G, Barroso I, Strachan DP, Deloukas P, Vollenweider P, Wareham NJ and Mooser V

    Lancet (London, England) 2008;371;9611;483-91


The research was funded by the Medical Research Council, Wellcome Trust, British Heart Foundation (BHF), European Commission, and GlaxoSmithKline.


GlaxoSmithKline one of the worlds leading research-based pharmaceutical and healthcare companies is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information and the companys product development pipeline, visit GSK at http://www.gsk.com/.

Medical Research Council

The Medical Research Council (MRC) supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all. http://www.mrc.ac.uk/.

British Heart Foundation

The British Heart Foundation (BHF) is the nations heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. But we urgently need help. We rely on donations of time and money to continue our life-saving work. Because together we can beat heart disease. For more information go to http://www.bhf.org.uk/.

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.


The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.


Sanger Institute Contact Information:

Don Powell Press Officer
Wellcome Trust Sanger Institute Hinxton, Cambs, CB10 1SA, UK

Tel +44 (0)1223 496 928
Mobile +44 (0)7753 7753 97
Fax +44 (0)1223 494 919
Email press.office@sanger.ac.uk

* quick link - http://q.sanger.ac.uk/3mwdhnnp