LONG AND SHORT Telomeres can tell whether you'll have heart disease, says study in The Lancet
SAN FRANCISCO A certain gene variant predisposes women to heart disease, a new US study has found, offering clues to the origins of heart attacks and strokes. Women with the gene variant were four times more likely to show signs of coronary-artery disease than women without, the researchers at Children's Hospital Oakland Research Institute in California said. Researchers relied on data the University of Iowa gathered through a continual study of 11,377 people since 1971 in Muscatine, Iowa. About 750 participants in the long-term study agreed to give DNA samples and comply with regular checkups over the years. Children's Oakland researchers identified the gene variant in female participants. About 77 percent of the women with the gene variant experienced early signs of heart attack and stroke. But the authors cautioned that because nearly all the participants were white, it's unclear whether the findings would prove true in other ethnic and racial groups. The study, published in the American Heart Association's journal Arteriosclerosis, Thrombosis and Vascular Biology, controlled for diet, smoking, and other risk factors. The research adds to the burgeoning field of genetics and personalized medicine, where people could learn early in life what diseases they are most susceptible to and make lifestyle choices to reduce risk.
PARIS Telomeres-nubby strips of DNA that cap the ends of chromosomes-predict a man's risk of developing heart disease, according to a study in The Lancet. Telomeres get shorter each time a cell divides. Shorter telomeres indicate older cells and are thus a marker of biological ageing, which varies according to the individual. British doctors measured the length of telomeres in the chromosomes of white blood cells among men aged 45 to 64 who had enrolled in a big study on coronary prevention in western Scotland. The 484 men who went on to develop coronary heart disease had shorter telomeres than the 1,058 men who remained disease-free, the investigators discovered. The same Scottish study also randomly assigned some volunteers to receive statins or placebo. The researchers found that in the placebo group, the risk of heart disease was almost double among the men with short telomeres compared with counterparts with long telomeres. But the good news was that in the statin group, those with short telomeres enjoyed a substantial cut in the risk of heart disease. The study says that measuring the length of telomeres in middle-aged men could help pinpoint those most at risk of heart disease and direct them to statin treatment.
PARIS The largest genetic investigation into autism has thrown up new clues about the inherited pathways for this disorder. In a paper published online by Nature Genetics, the Autism Genome Project (AGP) describe an innovative two-prong approach for trawling through the human genome to search for genetic susceptibilities. Researchers took samples from 1,168 families that had at least two autistic members, and ran a scan, looking for areas with common genetic mutations. They combined this with a screening of these families' DNA for so-called copy number variations (CNV)-small stretches of the genetic code that are poorly explored but which are believed to have minute insertions and deletions that cause illness. The work suggests that a previously unidentified region of chromosome 11 may be at fault, especially among females with autism, and also points the finger at genes responsible for neurexin, a protein important for communication between brain cells. Previous research in this field has identified regions on chromosomes 2, 7, and 17 as having a link with autism. The findings published by the AGP are preliminary data from the four-year-old project and need to be confirmed by further work. More than 120 researchers from at least 50 institutes in 19 countries are taking part in the AGP, a scheme launched in 2002.
CHICAGO US researchers have cloned mice using adult stem cells taken from the rodents' skin for the first time, according to a study that suggests this type of versatile cell can improve the success rate of this notoriously difficult procedure. Researchers have cloned mice before, using cumulus cells (cells that surround and support a developing egg) or fibroblasts (connective-tissue cells) and even some neural cells that were generated from embryonic stem cells. While successful, these efforts have also been notoriously inefficient, yielding a success rate of one to two percent on average. So for this experiment, researchers from Rockefeller University in New York and Howard Hughes Medical Institute in Chevy Chase, Maryland, used adult stem cells taken from the part of the hair follicle called the bulge which sits just below the skin. The cells are easily accessible, and because they have the capacity to self-renew and differentiate into other types of cells, the investigators suspected they might be a more promising candidate for nuclear transfer-the technique used to clone animals. In nuclear transfer, the nucleus of an unfertilized egg is substituted by the nucleus of another cell. The hybrid cells are cultured in the laboratory and then implanted in the mouse. The success rate with stem cells from female mice was on the order of 1.6 percent, which is similar to that seen in previous experiments, but when the cells came from male mice, the cloning attempts were successful in 5.4 percent of cases. "The efficiency of nuclear transfer is very low," said Jinsong Li, researcher at Rockefeller University. "Using purified adult skin stem cells as our source of nuclei, we have found that higher nuclear transfer efficiencies can be achieved." The study appears in the Proceedings of the National Academy of Sciences.
PARIS A tiny quirk in one of the human body's approximately 25,000 genes may be the culprit behind one of the world's most common and painful forms of arthritis. Among some 1,500 people tested in Japan, those carrying a particular variant of a protein-secreting gene called GDF5 were 80-percent more likely to develop osteoarthritis of the hip, according to a study published in Nature Genetics. The presence of the variant, lead author Yoshinari Miyamoto and a team of Japanese and Chinese researchers suggested, probably reduced the production of the GDF5 gene, which plays a key role in the development of cartilage in joints. A parallel sampling of populations in China and Japan also established a clear link between the same genetic irregularity and the incidence of knee arthritis, though the correlation was only half as strong. Sometimes called "wear-and-tear" arthritis because of the damage done to cartilage, osteoarthritis afflicts some 190 million people around the world, according to the World Health Organization. Ageing populations have increased the number of sufferers in the developed world as well, including more than 20 million in the United States. Arthritis is caused by the breakdown of cartilage, which acts as a cushion between bones that meet at a joint. Beyond a certain stage of disintegration, bone grates against bone, causing swelling, reduced mobility, and no small measure of pain. The onset of the condition typically occurs in males around the age of 45, and in females about some years later in life. The GDF5 gene, the authors explain, is "closely related to the subfamily of bone morphogenetic proteins known to be involved in joint formation." Earlier research on mice and humans has shown that mutations can cause abnormal development of the joints. To examine the association with hip arthritis, Miyamoto and his team sequenced DNA from 24 afflicted individuals and searched for variations in the genetic coding called SNPs (pronounced "snips") or single nucleotide polymorphisms. Nucleotides are chemical compounds that form the basic building blocks of DNA, which is 99 percent identical in all humans. SNPs occur when a single nucleotide in the genome differs between members of a species, or between paired chromosomes in a given individual. They account for about 90 percent of all human genetic variation. Once they had identified the suspect DNA sequence variations, they repeated the tests on a much larger group of osteoarthritis patients and on a control group, firmly establishing the link between the SNPs and the disease. The study is careful to note that the links established between the genetic variant and arthritis applied only to Asian populations. While it may apply more broadly, it is also true that a SNP common in one geographical or ethnic group may be much rarer in another.
NEW ORLEANS Doctors have rejuvenated post-heart-attack patients by injecting them with stem cells. In clinical trials, doctors delivered stem cells to hearts whose stiff, postattack scar tissue kept them from pumping blood as they should, according to the studies presented at the recent American College of Cardiology meeting in New Orleans, Louisiana. One of the trials used stem cells from bone marrow, a first for cardiology, according to the lead author Joshua Hare of the University of Miami in Florida. Among stem cells' many advantages is that they can be harvested from donors genetically dissimilar to the recipient, and they attach themselves at the point of an injury. Hare and his team injected intravenously 53 patients within 10 days of a heart attack. They randomly assigned patients different doses (0.5 million, 1.6 million, or 5.0 million cells per kilogram) and compared the dosages with a placebo. Over six months, the patients receiving the stem-cell treatment had better heart and lung function with fewer arrhythmias. Echocardiography also showed better heart function, especially in patients with greater heart damage. "This trial makes an important contribution in the field of stem-cell-based treatments for heart disease by providing safety and efficacy data for a unique and promising type of stem cell to treat cardiac damage," Hare said. "This study represents a first step. We must perform additional and larger trials to determine the real-world application of [marrow stem cells] to fight heart disease." The second study tested stem cells taken from the patients' own muscle tissue. Nabil Dib of the University of California led the team testing 23 patients with progressive, congestive heart failure. Researchers gave the control group of 11 patients standard drug treatments, while those in the treatment group received doses of 30 million, 100 million, 300 million, or 600 million muscular stem cells injected into their hearts. After six months the stem-cell recipients had markedly improved quality of life, while the control group worsened. "Transplantation using a minimally invasive catheter is safe, showed improvement in quality of life and may have the potential to improve cardiac function," Dib said. The US Food and Drug Administration will allow a phase-II randomized, double-blind, placebo-controlled clinical trial for up to 160 patients, he added. M |
