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
출처 : [Independent] Tuesday, 20 April 2010
http://www.independent.co.uk/news/science/how-genes-influence-obesity-senility-ndash-and-the-effects-of-olive-oil-1948818.html
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.”
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인간 유전자, 비만ㆍ노화에 영향
출처 : 연합뉴스 2010/04/20 11:37 송고
http://www.yonhapnews.co.kr/international/2010/04/20/0606000000AKR20100420105600009.HTML?template=2088
(서울=연합뉴스) 인간 게놈지도 초안이 완성된지 10년이 지난 현재 인간 건강에 대한 유전자의 복잡한 역할을 규명해주는 연구가 본격적으로 시작됐다고 영국 일간 인디펜던트 인터넷판이 20일 보도했다.
이날 세편의 관련 연구가 발표됐는데 한 연구는 비만과 연관된 유전자가 뇌기능 쇠퇴와도 관련이 있다는 내용, 또 한 연구는 특정 유전자가 노인들의 기억과 사고에 영향을 준다는 내용, 마지막 연구는 건강식인 지중해식 식사, 특히 천연 올리브유가 인간 게놈에 영향을 준다는 내용으로 되어있다.
지난 수십년 동안 과학자들은 인간의 건강과 심리적 기제에 영향을 주는 것이 환경과 교육인지, 유전인지에 대해 논쟁을 벌여왔다.
두 가지 모두 중요한 것으로 판명됐으나 유전자에 대한 환경의 영향이 인간 발전에 결정적인 역할을 하는 것으로 보인다. 인간 게놈은 어떻게 서로 다른 각각의 유전자들이 환경의 영향을 받아 서로 합쳐져 인간의 육체적, 정신적 건강에 작용을 하는지를 설명했다.
건강에 대한 다이어트의 예를 들면 지중해식 식사가 심장병, 뇌졸중, 심지어 치매의 위험을 낮춘다는 강력한 증거가 있다. 이때 중요한 것은 환경이다.
그러나 스페인 코르도바대학의 프란시스코 페레스-지메네스 교수는 천연 올리브 오일이 실제로 면역체계의 염증을 유발하는데 관련된 특정 유전자들에 영향을 줄 수 있다는 사실을 발견했다.
그는 대사 증후군 환자 20명을 상대로 6주에 걸쳐 한 그룹에는 페놀이 풍부한 천연 올리브유, 다른 그룹에는 저 페놀 올리브유를 아침식사에 제공했다. 과학자들은 이들의 유전자의 행동을 측정하고 천연 올리브유와 염증 유전자 억제 사이에 명백한 관련이 있다는 사실을 확인했다.
이 연구는 ‘BMC 게노믹스’에 실렸다.
한편 샌프란시스코의 캘리포니아대학 알렉산드라 피오코 교수는 70세에서 79세 사이의 노인 약 3천명을 상대로 주기적으로 기억력과 집중력 등 정신적 활동을 관찰하고 이들이 COMT 유전자의 두가지 유전적 변형 중 어떤 것을 갖고 있는지 알아보기 위해 DNA 검사를 실시했다.
이미 사고와 정신적 활동에 영향을 주는 것으로 알려진 COMT 유전자는 Val과 Met 두 형태로 구분되는데 연구 결과 Val 형태의 COMT 유전자를 가진 노인들은 Met 형태를 가진 노인들보다 노화에 따른 정신적 쇠퇴로부터 더 잘 보호되고 있었다.
이 연구는 ‘뉴롤로지’ 최근호에 게재됐다.
마지막 게놈관련 연구는 ‘전국과학아카데미회보’에 발표된 것으로, 로스앤젤레스 캘리포니아대학의 폴 톰슨 교수가 이끄는 연구팀은 치매 연구의 일환으로 200명의 건강한 노인의 뇌의 크기를 측정하고 DNA를 분석했으며 특히 FTO로 알려진 비만관련 유전자를 관찰했다.
연구결과 뇌의 크기 위축과 특정 형태의 FTO 유전자 사이에 명확한 관계가 나타났다.
나이가 들면서 비만이 인지기능 저하를 일으키는 위험 요소라는 것은 이미 알려진 사실이다.
연구팀은 뇌 위축 메커니즘이나 FTO 유전자가 이 과정에 어떤 작용을 하는지는 규명해내지 못했으나 FTO의 특정 형태가 몸무게의 단순한 영향에서 벗어나 뇌기능 저하에 하나의 원인이 된다는 것을 시사하는 충분한 증거가 있다고 밝혔다.
