Gene increases risks for smokers

Gene increases risks for smokers

News & Comment Left-handed risk? Whether you are right or left handed might affect your risk of developing inflammatory bowel diseases (IBD), such as...

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News & Comment

Left-handed risk? Whether you are right or left handed might affect your risk of developing inflammatory bowel diseases (IBD), such as Crohn’s disease or ulcerative colitis. Researchers at the Royal Free and University College Hospital Medical School (London, UK) studied 17 000 people born in the UK between 1958 and 1970, and found that left handers were twice as likely to develop IBD than right-handed individuals. Left handedness has been previously linked with various autoimmune diseases, including asthma and diabetes. The reasons for the association of handedness with certain disorders are unknown and controversial. The authors of the study, published in July in the journal Gut, cite observed seasonal variations in left-handed births and environmental factors, as possible explanations. JW

Cloned mice: genetically ‘unstable’ Subtle genetic abnormalities have been identified in apparently healthy cloned mice, generating further doubts over the safety of any future cloned human tissues. A team of geneticists led by Rudolf Jaenisch (Whitehead Institute for Biomedical Research, MA, USA) discovered ‘widespread dysregulation’ of certain genes in mice cloned from embryonic stem cells and by nuclear transfer. Their results, published in Science in July, suggest that mammalian development is more tolerant than previously believed to aberrant gene regulation. However, it seems likely that subtle changes in physiology or behaviour will be present in some, if not all, cloned mammals, and these anomalies could be difficult to detect. PoN

Apoptotic cells resurrected Researchers examining the process of cellular suicide, apoptosis, in nematode worms have stumbled upon something remarkable – it is reversible. This form of ‘programmed cell death’ allows cells to be removed discretely from tissues without

TRENDS in Molecular Medicine Vol.7 No.9 September 2001

spillage of cellular content, as occurs following necrosis. The dying cells form characteristic ‘apoptotic bodies’ and are removed from the scene by phagocytosis. Now, two articles, appearing in Nature, reveal that if apoptotic bodies are not ‘eaten’ by phagocytes, they can recover fully from their ordeal. These results implicate the ‘corpse-clearing’ cells themselves as being important in ensuring the apoptotic pathway is completed, and indicate that the initial steps involved can be reversed. Apoptosis is a normal and necessary biological process and is also implicated in disease states such as ischaemia, and many neurodegenerative conditions. It is speculated that inhibition of phagocytosis could be of therapeutic benefit in such circumstances. PoN


protein – in the test case, insulin. Although expression of the transgene is transient, lasting only a few days, Michael German (UCSF), one of the inventors of the ‘gene pill’, is hopeful that this is a step toward treatment of diabetes and other diseases of blood-secreted proteins, commenting ‘Regular oral delivery of new genes would provide continuous production of insulin, and the natural removal of the affected cells would permit doses to be adjusted or stopped easily.’ AR

Gene increases risks for smokers

Gene array breakthrough for glioblastoma The application of new gene array technology has provided valuable new leads in the battle to understand, and hopefully treat, glioblastoma multiforme (GBM), a malignant and deadly brain tumour. Using gene array technology, researchers were able to simultaneously investigate the expression of more than 11 000 genes. Lead author of the work, Julia Ljubimova (Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center, CA, USA), detected overexpression of 14 genes, confirming previous work and opening new avenues for exploration. One of the most promising new discoveries was the enhanced levels of laminin-8 found in GBM samples. Ljubimova’s team believes laminin-8 could be critical in the progression of the condition to malignancy, possibly by affecting the tumours blood supply. Time will tell if these data, published in July’s Cancer Research, will lead to the development of new treatment strategies for this condition. PoN

‘Gene pill’ extended to blood proteins A new patent for a method of delivering normal genes in pill form was granted in July in the USA, to include proteins that are secreted into the bloodstream. Researchers from the University of California, San Francisco (UCSF) (CA, USA) successfully demonstrated delivery of raw DNA taken orally into intestinal cells, and this prompted these cells to produce the appropriate

A recent study conducted at Royal Free and University College London Medical School, UK has identified a specific allele of the APO-E gene that significantly elevates the risk of heart disease in smokers. Led by Professor Steve Humphries, the research team monitored the health of >3000 middleaged men over a period of 8 years. They discovered that smokers carrying the E4 form of the gene were 4-times more likely to develop cardiovascular problems than nonsmokers. APO-E encodes apolipoprotein E – a protein critical in preventing oxidation of LDL cholesterol; the E4 version appears to be least effective in this role. Although up to a quarter of the UK male population carries the E4 allele, placing them at greater risk, Humphries does not advocate the development of a risk-assessing genetic test. Cessation of smoking remains the most effective method of risk reduction. PoN

Jonathan Weitzman [email protected] Paul O’Neill [email protected] Adam Rutherford [email protected]

1471-4914/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.