UK scientists, including Tim Spector, Professor of Genetic Epidemiology at King’s, are to mount the world’s first search of the human genome for genetic risk factors for osteoarthritis.

ARC Press Release – 12 October 2007

On World Arthritis Day (October 12) the Arthritis Research Campaign (arc) has announced plans to run a definitive genome-wide association study of osteoarthritis susceptibility called arcOGEN; the largest study of its kind ever undertaken. The study will involve screening the DNA of 8,000 people suffering from osteoarthritis of the hip and knee and 6,000 healthy people to compare the differences.

The aim of the arcOGEN study is to identify the genetic changes, known as polymorphisms, that increase the risk of people developing osteoarthritis. The charity expects that this could lead to several potential breakthroughs such as genetic tests becoming available to predict who is likely to develop osteoarthritis, particularly at a young age, and how severely. Ultimately it could lead to new drugs that could slow down disease progression and even prevent osteoarthritis occurring.

The two-year study will be funded by a grant of £2.2 million: the largest single grant ever awarded by the medical research charity.

Osteoarthritis (OA) is the most common type of arthritis, affecting more than two million older people in the UK, causing pain and stiffness as the cartilage at the ends of bones wears away. It can affect any joints but involvement of the knee and hip is the number one cause of mobility problems in the elderly population. Despite its high prevalence there is no effective drug treatment to control the progression of osteoarthritis, and currently available painkillers carry a high risk of side effects.

Wrongly thought of as an inevitable consequence of ageing, osteoarthritis is a disease in its own right but the reasons why some people do, and some do not develop the disorder are unclear.

Debilitating disease

‘Osteoarthritis is an extremely debilitating disease characterised by joint pain and reduced mobility, and is the biggest cause of disability in older people bar none,’ explained Dr John Loughlin, principal investigator of the arcOGEN study, and a geneticist from the Nuffield Department for Orthopaedic Surgery at the University of Oxford.

‘Genetic factors play a major role in the development of OA and identifying them will help us to understand why the disease occurs and will assist in the development of new treatments by identifying new molecular targets. We have brought together all the major OA genetics research groups within the UK and experts in human genetics to enable us to perform the definitive search of the human genome for OA genetic risk factors.’

Professor Alan Silman, medical director of the Arthritis Research Campaign, said that arcOGEN could be the most important study the charity had ever funded and could have far-reaching consequences in terms of better understanding of the disease and identifying new treatment targets.

‘Compared with many other conditions where scientists have looked for a genetic basis, there is a very strong belief that OA is genetically-based because there are many families which have OA running through the generations,’ he said. ‘Until now we didn’t know what that genetic basis was, but now we have the modern technology we have a unique opportunity to unlock the genetic code.’

It is known that there is a considerable genetic component to osteoarthritis, and those people with a parent or sibling with the condition are two to three times more likely to develop OA than those who don’t. However, there are also other risk factors such as obesity, a sports injury or a heavy manual occupation. It may become possible for medics to perform a genetic-risk profile alongside a lifestyle-risk profile to determine the overall risk, and then offer treatment or advice on how the risk could be reduced.

Another leading member of the consortium, Tim Spector, Professor of Genetic Epidemiology and Director of the Twin Research Unit at King’s College London, said that the consortium’s investigation of the DNA of 8,000 patients would provide it with ‘unprecedented power’. The results would be made freely available as an international resource that could be mined for insights into new treatments. The outcome of the genome screen is likely to be of considerable interest to pharmaceutical companies wanting to develop new drugs to prevent the onset of osteoarthritis. Identifying predisposing genes will point out new biological pathways to target.

The arcOGEN team hope to find between ten and 20 of the genes that could have a strong to moderate risk for osteoarthritis, although there may be many more. Human DNA contains about 30,000 genes, with millions of polymorphisms, which will all be checked by sampling patients’ DNA taken from their white blood cells.

Genetics experts in London, Oxford, Manchester, Southampton, Nottingham, Edinburgh, Newcastle and Cambridge will form part of the UK-wide collaborative project.

For more information contact: Jane Tadman, Press Officer, Arthritis Research Campaign, tel: 01246 541107; mobile: 07974 203828; email: j.tadman@arc.org.uk

Notes to editors

The Arthritis Research Campaign (arc) is the fourth largest medical research charity in the UK, raising more than £30 million in 2006/7 entirely from public donations. It currently funds more than 350 research projects into all types of arthritis and musculoskeletal conditions in medical schools and hospitals around the UK, and also has an extensive educational remit. For more information about the work of the charity go to www.arc.org.uk

The Twin Research Unit, based at St Thomas’ Hospital, has a database of 10,000 twins and studies a wide variety of diseases and traits and is always looking for more adult twin volunteers, male or female, identical or non-identical to help with their studies. To volunteer or for more information please phone: 020 7188 5555 or visit the website.

Further information
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People with large numbers of moles may age slower than expected, according to a study from King’s. Researchers studied the skin and telomere length (a marker of biological ageing found on all cells in the body) of more than 1800 twins and found that people with a high number of moles had longer telomeres.

The 10 year study from the Twin Research Unit was funded by the Wellcome Trust and is published in the July edition of Cancer Epidemiology Biomarkers & Prevention.

Moles appear in childhood and disappear from middle age onwards. When present in large numbers they can increase the risk of melanoma, a rare form of skin cancer. Moles vary significantly in numbers and size between individuals. The average number of moles in people with white skin is 30 but some people may have as many as 400. Some moles may be 2mm in diameter whilst others are well over 5mm. The reason for such differences between people is unknown as is the function of moles. Doctors have suspected that people with lots of moles may have some advantages in view of the fact that moles are common in the general population. The Twin Research Unit has already shown in a previous study on over 2000 twins that up to 60 per cent of susceptibility to moles is inherited.

Since moles disappear with age, scientists at the Twin Research Unit looked at the relationship between the number of moles and telomere length, which is a good indicator of our rate of ageing. Telomeres, which get shorter as we age, are bundles of DNA found at the end of chromosomes in all cells and assist in the protection, replication, and stabilization of the chromosome ends. (Telomeres have been compared with the plastic tips on shoelaces because they prevent chromosome ends from fraying and sticking to each other). A measure of the telomere length in white cells in the blood has been found to correlate with ageing in many different organs such as heart, muscle, bones and arteries.

The researchers compared telomere length measurements in white cells with the number of moles in more than 1800 female twins (900 pairs of twins) aged between 18 and 79 years. They found that those with high numbers of moles (greater than 100) had longer telomeres than those with very few moles (fewer than 25). The difference between the two mole groups was equivalent to six to seven years of normal ageing (estimated by looking at the average rate of telomere length loss per year in the whole group). This was not affected by other factors such as age, weight or smoking.

These results suggest those with higher numbers of moles may have a delayed ageing as they have longer telomeres and appear to keep their moles for longer. In contrast, people with shorter telomeres have lower numbers of moles and appear to lose them quicker with age – which may be a marker of accelerated ageing.

Lead researcher Dr Veronique Bataille says: ‘The results of this study are very exciting as they show, for the first time, that moley people who have a slightly increased risk of melanoma may, on the other hand, have the benefit of a reduced rate of ageing. This could imply susceptibility to fewer age-related diseases such as heart disease or osteoporosis, for example. Further studies are needed to confirm these findings.’

Professor Tim Spector, Head of the Twin Research Unit and co-author of the study, adds: ‘We now plan to look in more detail at the genes which influence the numbers of moles and to see whether they may also slow down the ageing process in general. We’ll examine the rate of ageing in the skin, muscles and bones in different groups according to their mole counts.’

Notes to editors

The Twin Research Unit at King’s College London has a database of 10,000 twins and studies a wide variety of diseases and traits and is always looking for more adult twin volunteers, male or female, identical or non-identical to help with their studies. To volunteer or for more information please phone: 020 7188 5555 or visit the website:www.twinsUK.ac.uk

King’s College London

King’s College London is the fourth oldest university in England with more than 13,700 undergraduates and nearly 5,600 graduate students in nine schools of study based at five London campuses. It is a member of the Russell Group: a coalition of the UK’s major research-based universities. The College has had 24 of its subject-areas awarded the highest rating of 5* and 5 for research quality, demonstrating excellence at an international level, and it has recently received an excellent result in its audit by the Quality Assurance Agency.

King’s has a particularly distinguished reputation in the humanities, law, international relations, medicine, nursing and the sciences, and has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA. It is the largest centre for the education of healthcare professionals in Europe and is home to five Medical Research Council Centres – more than any other university.

King’s is in the top group of UK universities for research earnings, with income from grants and contracts of more than £100 million, and has an annual turnover of more than £363 million.

Wellcome Trust

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

Further information
Public Relations Department
Email: pr@kcl.ac.uk
Tel: 020 7848 3202