Researchers at King’s College London have investigated a new method that could be used by GPs to quickly determine the number of moles on the entire body by counting the number found on a smaller ‘proxy’ body area, such as an arm.

Naevus (mole) count is one of the most important markers of risk for skin cancer despite only 20 to 40 per cent of melanoma arising from pre-existing moles. The risk is thought to increase by two to four per cent per additional mole on the body, but counting the total number on the entire body can be time consuming in a primary care setting

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Our latest research in collaboration with the University of East Anglia shows that a diet high in proteins is as beneficial as exercise for our cardiovascular health. The researchers analysed diet and clinical measures from 2000 of our twins and found evidence that showed that high levels of aminoacids had a positive effect on blood pressure and arterial stiffness.

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A new study has identified the key genes involved in the breadth of our immune response that may influence our susceptibility to diseases such rheumatoid arthritis, leprosy and malaria.

The study, led by King’s College London and the US National Institutes of Health (NIH), suggests much of our immune system is under the control of our genes and may explain why autoimmune disorders run in some families and others are more susceptible to infections.

Our immune system has evolved over millions of years into a remarkable defence mechanism offering us rapid protection from major environmental threats and pathogens. However, despite recent discoveries of genetic variants associated with autoimmunity and infection, how our genes control critical components of our immune system has remained poorly understood up to now.

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British Gut – an innovative UK open-source science project to understand the microbial diversity of the human gut – is launched today by the Department of Twin Research at King’s College London, in collaboration with American Gut.

This cutting edge science project will give people in the UK and across Europe the opportunity to be science makers and learn more about the microbes which live in their gut, skin and mouth. They will also find out how their microbes are affected by their own diet and lifestyle.

Research has shown that the 100 trillion bacteria living naturally in the gut play an important role in human health and disease. Each individual’s bacteria are unique to him or her, and small changes in this finely balanced community can influence susceptibility to illnesses such as Irritable Bowel Syndrome, cancer, heart disease and obesity.

British Gut aims to create a large resource of samples and data available to scientists. Volunteers are invited to donate to the project, after which they will receive a swab kit to collect a sample of their gut microbes to be sent to King’s. British Gut will then sequence the genetic sample, provide participants with a list of the bacteria present in their gut, and map how it compares to the rest of the population sampled.

The Department of Twin Research at King’s is home to TwinsUK, the biggest UK adult twin registry with 12,000 twins and one of the leading UK Microbiome centres, which has already identified significant differences in the types of microbes people have in their gut. Research at Twins UK has also shown that both identical and non-identical twins only share around 50 per cent of bacterial groups. Future studies now need to identify their role and how researchers can influence bacteria to improve our health and general wellbeing.

Professor Tim Spector, Head of the Department of Twin Research and Genetic Epidemiology at King’s and lead investigator for British Gut, said: Many differences between people may be genetic. ‘Participants in American Gut and now British Gut can test how different diets shape their bodies. This is an exciting time to map our own personalised microbes – which appear to be key for health and longevity, but also for many common diseases. This is a great opportunity for British citizen scientists to find out about their own bodies and diets – whilst also benefiting science.’

A recent pilot study led by British Gut showed that diets can change gut microbial diversity, even within a few days. Dietary interventions included a cheese and yogurt-heavy diet, dietary cleanses using only plant foods, and fasting. The dietary interventions, especially the more dramatic cleanses and fasts, did induce changes, but not in the same way in different individuals. Professor Rob Knight, co-founder of American Gut, said: ‘Unlike our human genomes, which are all more than 99 per cent the same, our microbiomes are mostly very different from one another. These microbial differences may explain why our bodies respond differently to different diets, but may ultimately help us predict which diets will work for which people.’

Interestingly, some people experienced more dramatic changes than others. ‘These results show that the effect of a dietary intervention – and the ability to detect an effect against background variation – varies from person to person,’ said Dr Luke Thompson, also of American Gut.

The data are freely available to access online. For further information visit the British Gut website: http://www.britishgut.co.uk/

Researchers at King’s College London and Imperial College London have discovered that people with fewer copies of a gene coding for a carb-digesting enzyme may be at higher risk of obesity. The findings, published in Nature Genetics, suggest that dietary advice may need to be more tailored to an individual’s digestive system, based on whether they have the genetic predisposition and necessary enzymes to digest different foods.

Salivary amylase plays a significant role in breaking down carbohydrates in the mouth at the start of the digestion process. The new study suggests that people with fewer copies of the AMY1 gene have lower levels of this enzyme and therefore will have more difficulty breaking down carbohydrates than those with more copies.

Previous research has found a genetic link between obesity and food behaviours and appetite, but the new discovery highlights a novel genetic link between metabolism and obesity. It suggests that people’s bodies may react differently to the same type and amount of food, leading to weight gain in some and not in others. The effect of the genetic difference found in the latest study appears much stronger link than any of those found before.

Researchers first measured gene expression patterns in 149 Swedish families with differences in the levels of obesity and found unusual patterns around two amylase genes (AMY1 and AMY2), which code for salivary and pancreatic amylase. This was suggestive of a variation in copy numbers relating directly to obesity.

The finding was replicated strongly in 972 twins from TwinsUK, the biggest UK adult twin registry, which found a similar pattern of expression. The researchers then estimated the precise copy numbers of the amylase gene in the DNA of a further 481 Swedish subjects, 1,479 subjects from TwinsUK and 2,137 subjects from the DESIR project.

The collaborative team found that the number of copies of the AMY1 gene (salivary amylase) was consistently linked to obesity. Further replication in French and Chinese patients with and without obesity showed the same patterns.

A lower estimated AMY1 copy-number showed a significantly increased risk of obesity in all samples and this translated to an approximate eight-fold difference in the risk of obesity between those subjects with the highest number of copies of the gene and those with the lowest.

Standard Genome wide mapping methods (GWAS) had missed this strong association as the area is technically hard to map. This variation in copy numbers, also known as ‘copy number variants’ (CNV) has been underestimated as a genetic cause of disease, but the link between CNV in the amylase gene and obesity provides an indication that other major diseases may be influenced by similar mechanisms.  

Professor Tim Spector, Head of the Department of Twin Research and Genetic Epidemiology at King’s and joint lead investigator said: “These findings are very exciting. While studies to date have mainly found small effect genes that alter eating behaviour, we discovered how the digestive ‘tools’ in your metabolism  vary between people – and the genes coding for these – can have a large influence on your weight.

“The next step is to find out more about the activity of this digestive enzyme, and whether this might prove a useful biomarker or target for the treatment of obesity.

“In the future, a simple blood or saliva test might be used to measure levels of key enzymes such as amylase in the body and therefore shape dietary advice for both overweight and underweight people. Treatments are a long way away but this is an important step in realising that all of us digest and metabolise food differently – and we can move away from ‘one-size fits all diets’ to more personalised approaches.” 

-ends-

Professor Spector is available for interview on Friday 28 March 2014. For further information please contact the Hannah Pluthero at King’s College London, on 0207 848 3202 or email hannah.l.pluthero@kcl.ac.uk

Notes to editors:

King’s College London

King’s College London is one of the top 20 universities in the world (2013/14 QS World University Rankings), and the fourth oldest in England. It is The Sunday Times ‘Best University for Graduate Employment 2012/13’. A research-led university based in the heart of London, King’s has more than 25,000 students (of whom more than 10,000 are graduate students) from nearly 140 countries, and some 6,500 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: www.kingshealthpartners.org.

Researchers at King’s College London have discovered that sensitivity to pain could be altered by a person’s lifestyle and environment throughout their lifetime. The study is the first to find that pain sensitivity, previously thought to be relatively inflexible, can change as a result of genes being switched on or off by lifestyle and environmental factors – a process called epigenetics, which chemically alters the expression of genes.

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Scientists have found that key metabolites in blood – chemical ‘fingerprints’ left behind as a result of early molecular changes before birth or in infancy – could provide clues to a person’s long-term overall health and rate of ageing in later life.

Published today in the International Journal of Epidemiology, the study of twins led by King’s College London highlights how a technique called metabolomic profiling has revealed a collection of 22 metabolites linked to ageing. One of these, linked to ageing traits such as lung function and bone mineral density, is also strongly associated with birthweight – a well-known developmental determinant of healthy ageing.

This finding suggests that levels of this novel metabolite, which may be determined in the womb and affected by nutrition during development, could reflect accelerated ageing in later adult life.

Scientists say the findings show it is possible that these markers of ageing can be identified with simple blood tests in the future, which may provide further clues to the ageing process and could pave the way for development of therapies to treat age-related conditions.

Professor Tim Spector, Head of the Department of Twin Research at King’s College London, said: ‘Scientists have known for a long time that a person’s weight at the time of birth is an important determinant of health in middle and old age, and that people with low birthweight are more susceptible to age related diseases. So far the molecular mechanisms that link low birthweight to health or disease in old age had remained elusive, but this discovery has revealed one of the molecular pathways involved.’

Funded by the European Commission, Researchers from the Department of Twin Research at King’s carried out metabolomic profiling – the study of metabolites that specific cellular processes or changes leave behind in the blood. Analysing blood samples donated by over 6,000 twins, they identified 22 metabolites directly linked to chronological age – the concentrations of the metabolites were higher in older people than in younger people.

One particular metabolite – C-glyTrp – is associated with a range of age-related traits such as lung function, bone mineral density, cholesterol and blood pressure. Its role in ageing is completely novel.

Crucially, researchers found it was also associated with lower weight at birth when they compared the birth weights of identical twins.

To explore the link between birthweight and the metabolite, the researchers showed via genetic tests that the gene influencing the levels could be modified epigenetically (whereby genes are switched on or off by chemical switches triggered by the person’s environment or lifestyle). These epigenetic changes may then influence metabolism during a person’s lifetime, which in turn influences their risk of age-related diseases.

Ana Valdes, lead researcher from King’s, said: ‘Human ageing is a process influenced by genetic, lifestyle and environmental factors, but genes only explain a part of the story. Molecular changes that influence how we age over time are triggered by epigenetic changes. This study has for the first time used analysis of blood and epigenetic changes to identify a novel metabolite that has a link to birthweight and rate of ageing.

‘This unique metabolite, which is related to age and age related diseases, was different in genetically identical twins that had very different weight at birth. This shows us that birthweight affects a molecular mechanism that alters this metabolite. This may help us understand how lower nutrition in the womb alters molecular pathways that result in faster ageing and a higher risk of age-related diseases fifty years later.

‘Understanding the molecular pathways involved in the ageing process could ultimately pave the way for future therapies to treat age-related conditions. As these 22 metabolites linked to ageing are detectable in the blood, we can now predict actual age from a blood sample pretty accurately and in the future this can be refined to potentially identify future rapid biological ageing in individuals.’

For further information or a copy of the paper please contact Emma Reynolds, PR Manager (Health) at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk

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