How genes influence obesity, senility – and the effects of olive oil

The genome has allowed scientists to shed new light on some of the most intractable medical conditions. Steve Connor reports
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The Independent Online

In 2000 President Bill Clinton and Prime Minister Tony Blair announced in a joint satellite broadcast from the White House and Downing Street that scientists had completed the first draft of the human genome. Ten years on and medical researchers are now enjoying a 'genome bonanza' that has begun to elucidate the complex role of genes in human health.

Three such studies are published today. One describes how a gene linked to obesity is also associated with mental deterioration, a second shows how another gene affects memory and thinking in old age and the third study identifies the part of the human genome affected by a healthy Mediterranean diet – or more specifically virgin olive oil.

When the draft genome was published, President Clinton ruffled a few atheistic feathers when he suggested that the milestone represents the translation of a mysterious code designed by a higher being. "Today, we are learning the language in which God created life," he said.

Whether God-given or not, it took another three years for scientists to finally complete the entire 'book of life', as the human genome came to be called. And it was soon clear that as a powerful research tool it would unleash untold insights into the workings of the human body, as well as our relationships to the wider living world.

The genome contains the entire digital recipe for making a human being. It consists of three billion individual letters of the genetic alphabet, arranged in a sequence that is unique to each person, which includes approximately 23,000 human genes that determine the production of the proteins, cells and tissues of the body.

For decades, biological science argued abut "nature versus nurture". Is environment and upbringing the important influence that determines a person's health and psychological makeup, or is it in the genes that they have inherited?

It turns out that both are important but more interestingly it is the influence of the environment on the genes that appears to play a decisive role in how people develop. The human genome has shown how a disparate variety of individual genes combine together, along with environmental influences, to affect a person's physical and mental well-being.

Take the influence of diet on health. There is strong evidence to suggest that a Mediterranean diet lowers the risk of heart disease, stroke and even Alzheimer's disease. This is the environment at work. But a study by Francisco Perez-Jimenez from the University of Cordoba in Spain, published in the journal BMC Genomics, shows how virgin olive oil can actually influence certain genes involved in triggering inflammatory processes of the immune system.

Professor Perez-Jimenez took 20 patients with metabolic syndrome, which is linked with heart disease and type-2 diabetes, and fed them for six weeks with two types of breakfast, one with virgin olive oil, which is rich in substances called phenols, and the other with low-phenol olive oil. As the experiment unfolded, the scientists tested the activity of the volunteers' genes and found a clear association between virgin olive oil and the suppression of the inflammatory genes.

"We identified 98 differentially expressed genes when comparing the intake of phenol-rick olive oil with low-phenol oil. Several of the repressed genes are known to be involved in pro-inflammatory processes, suggesting that the diet can switch the activity of the immune system to a less deleterious inflammatory profile, as seen in metabolic syndrome," Professor Perez-Jimenez said. "These findings strengthen the relationship between inflammation, obesity and diet and provide evidence at the most basic level of healthy effects derived from virgin olive oil consumption in humans."

But it is not just physical health that is benefiting from understanding the human genome. A number of studies into the genes involved in brain development and function are helping to revolutionise our understanding of human cognition and mental health.

Alexandra Fiocco at the University of California, San Francisco, led a study of nearly 3,000 people aged between 70 and 79 who were regularly tested for mental performance, specifically memory and concentration. Their DNA had also been tested to see which of two genetic variants of a gene called COMT the volunteers were carrying.

The COMT gene, which was already known to influence thinking and mental performance, comes in two forms, or alleles, called Val and Met. The study, published in the journal Neurology, demonstrated that elderly people with the Val version of the gene seemed to be better protected against mental decline as they got older compared to people carrying the Met version of the COMT gene.

"This is the first study to identify a protective relationship between this gene variant and cognitive function. This finding is interesting because in younger people, the Val genotype has been shown to have a detrimental effect," Dr Fiocco said. "But in our study of older people, the reverse was true. Finding connections between this gene, its variants and cognitive function may help scientists find new treatments for the prevention of cognitive decline."

The third genome-related study, published in the Proceedings of the National Academy of Sciences, investigated 200 healthy, elderly people whose brains were scanned as part of research into Alzheimer's disease. In addition to measuring their brains, scientists also analysed their DNA, specifically a gene known to be involved in obesity, called fat mass and obesity associated (FTO) gene.

What emerged was a clear association between diminished brain volume – or atrophy – and a certain version of the FTO gene. It was already known that obesity is a risk factor for cognitive decline in older age, and it has been previously associated with detectable differences in the brain volume of overweight people.

The researchers, led by Paul Thompson of the University of California, Los Angeles, could not identify the mechanism causing the brain atrophy, or how the FTO might influence this process. However, they believe there is enough evidence to suggest that the particular variant of the FTO contributes to brain deterioration beyond the simple influence of a person's body weight.

The FTO gene, sometimes called the "fatso" gene, has emerged from the genome project as a leading genetic influence in obesity. It seems to account for a substantial proportion of obesity cases.

In 2007, for instance, scientists found a genetic variation of the FTO gene that gives a child a 70 per cent higher risk of developing obesity compared to a child with another version of the gene. It was the first real insight into why some people are born with a predisposition to putting on weight, while others stay slim even in a high-calorie environment.

"Even though we have yet to fully understand the role played by the FTO gene in obesity, our findings are as source of great excitement," said Professor Mark McCarthy of Oxford University. "By identifying this genetic link, it should be possible to improve our understanding of why some people are more obese, with all the associated implications such as increased risk of diabetes and heart disease."

Shortly before that study was published, another research team analysed the genetic factors that may play a role in determining whether someone is likely to be able to give up smoking or not. It found that people who tried to give up and failed were much more likely to have inherited a series of genetic traits compared to successful quitters. Scientists screened more than 520,000 genes from hundreds of smokers who had tried to quit. The screening eventually led to 221 genes that distinguished successful from unsuccessful quitters. Many of these genes were already associated with addiction and drug dependence.

Nora Volkow, director of the US National Institute on Drug Abuse in Washington, said the study marked the first time that scientists had been able to identify the genes involved in the ability to stop smoking. She said: "These findings lend further support to the idea that nicotine dependence shares some common genetic vulnerabilities with addictions to other legal and illegal substances."