Science News & Science Current Events
 
Email a Friend Send to a friend
Printer Friendly Print Variations in detoxifying genes linked to Lou Gehrig's disease

Variations in detoxifying genes linked to Lou Gehrig's disease

July 06, 2006

Genetic variations in three enzymes that detoxify insecticides and nerve gas agents as well as metabolize cholesterol-lowering statin drugs may be a risk factor for developing sporadic amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), and possibly responsible for a reported twofold increased risk of ALS in Gulf War veterans.

These findings, from a study led Teepu Siddique, M.D., and colleagues at Northwestern University, open the door to investigating gene-environment interactions as a cause of ALS and other illnesses and to the development of molecular targets for specific treatments. The study was published in the August 22 online issue (available now) of the journal Neurology.




Siddique is Les Turner ALS Foundation/Herbert C. Wenske Professor, Davee Department of Neurology and Clinical Neurosciences, professor of cell and molecular biology and director of the Neuromuscular Disorders Program at Northwestern University Feinberg School of Medicine.

ALS is a complex neurodegenerative disorder of the motor neurons that results in muscle weakness, difficulty speaking, swallowing and breathing and eventual total paralysis and death generally within five years.

In 1993 Siddique and collaborators determined that mutations in a gene known as SOD1 account for 20 percent of familial, or inherited, ALS (2 percent of all cases of ALS). However, the cause of sporadic ALS is still unknown.

In earlier research Siddique and other researchers hypothesized that sporadic ALS is modulated by variations in multiple genes interacting with each other and environmental exposures.

The genes for human paraoxanases (PON 1, PON 2 and PON 3), which are located on chromosome 7q21.3, code for the production of detoxifying enzymes involved in the metabolism of a variety of drugs, organophosphate insecticides, such as parathion, diazinon and chlorpyrifos, and nerve gas agents such as sarin.

Previous research described a possible twofold increased risk for developing ALS in veterans of the Gulf War, indicating a war-related environmental exposure to organophosphates and sarin in genetically susceptible individuals as a possible cause. PON gene cluster variants have previously been associated with other neurodegenerative and vascular disorders, including Alzheimer's disease, Parkinson's disease, coronary artery disease and stroke.

Although the Northwestern DNA study samples were not analyzed for inclusion of Gulf War veterans, Siddique and co-researchers found significant evidence that gene variations (polymorphisms) on the chromosome region encompassing PON2-PON3 were strongly associated with sporadic ALS.

"Thus, single nucleotide polymorphism genotyping in the intergenic regions of the PON gene cluster, and replication, gene expression, gene-gene interaction and PON serum/enzymatic studies may help elucidate the complexity of PON cluster association with ALS," Siddique said.

Siddique hopes to study DNA samples from Gulf War veterans with increased incidence of sporadic ALS and has applied for their DNA from the Veterans Administration collection.

Northwestern University



Related ALS Current Events and ALS News Articles ALS Current Events and ALS News RSS ALS Current Events and ALS News RSS
The Structure of the Mre11 Protein Bound to DNA
Repairing breaks in the two strands of the DNA double helix is critical for avoiding cancer. In humans and other organisms, a molecular machine called the MRN complex is responsible for finding and signaling double-strand breaks (DSBs), then launching the error-free method of DNA repair called homologous recombination.

Study findings help EMS respond to cardiac arrest emergencies more safely and efficiently
When cardiac arrest patients cannot successfully be resuscitated by emergency medical services in the field, lifesaving attempts to race them to a nearby hospital via ambulance often prove to be futile.

Tracking Down the Menace in Mexico City Smog
A new report by scientists who are part of the international MILAGRO Campaign indicates that some of the most harmful air pollution in Mexico City may not come from motor vehicles but instead originates with industrial sources - and that the culprit may be garbage incineration.

Data mining detects signs of Lou Gehrig's disease in gene carriers long before symptoms appear
Inspired by the use of microarray chips that look for gene combinations, psychologists are using "pattern array" software to spot movements in rats that might help them predict diseases such as Lou Gehrig's syndrome.

Protein plays Jekyll and Hyde role in Lou Gehrig's disease
Amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig's disease, is a fatal neurodegenerative disease caused by the death of motor neurons in the brain and spinal cord that control muscle movements from walking and swallowing to breathing. In a groundbreaking study this week in PLoS Biology, Brandeis and Harvard Medical School scientists report key findings about the cause and occurrence of the familial form of ALS.

New study of gene evolution could lead to better understanding of neurodegenerative disease
Genetic evolution is strongly shaped by genes' efforts to prevent or tolerate errors in the production of proteins, scientists at The University of Texas at Austin and Harvard University have found.

Researchers probe geographical ties to ALS cases among 1991 Gulf War veterans
Researchers from Duke University, the University of Cincinnati (UC) and the Durham Veterans Administration Medical Center are hoping to find a geographical pattern to help explain why 1991 Gulf War veterans contracted the fatal neurological disease amyotrophic lateral sclerosis (ALS) at twice the normal rate during the decade after the conflict.

Umbilical cord blood cell transplants may help ALS patients
A study at the University of South Florida has shown that transplants of mononuclear human umbilical cord blood (MNChUCB) cells may help patients suffering from Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease.

Lou Gehrig's protein found throughout brain, suggesting effects beyond motor neurons
Two years ago researchers at the University of Pennsylvania School of Medicine discovered that misfolded proteins called TDP-43 accumulated in the motor areas of the brains of patients with amyotropic lateral sclerosis (ALS), or Lou Gehrig's disease.

UC San Diego Physicists Reveal Secrets of Newest Form of Carbon
Using one of the world's most powerful sources of man-made radiation, physicists from UC San Diego, Columbia University and Lawrence Berkeley National Laboratory have uncovered new secrets about the properties of graphene-a form of pure carbon that may one day replace the silicon in computers, televisions, mobile phones and other common electronic devices.
More ALS Current Events and ALS News Articles
EMS Field Guide: ALS Version
by Paul Lesage, Paula Derr, Jon Tardiff

The Seventeenth Edition EMS Field Guide® ALS version has been updated with the latest CPR and ACLS algorithms from the AHA. This handy guide makes it easy for paramedics, nurses and physicians to look up their patients' medications, check drug doses, quickly interpret 12-Lead EKGs and much more! At only 3"x5" it easily fits in your pocket, has color-coded tabs, and is waterproof, alcohol-fast...



ALS Network+ Certification Package (Microsoft Official Academic Course Series)
by Microsoft Official Academic Course

Competency-based learning for the academic classroom. Developed for academic courses, A+ CERTIFICATION, Fourth Edition, helps students build the skills they need on the job and for the CompTIA A+ Core Hardware and Operating System Technologies exams. The textbook delivers courseware adaptable for either a full 16-week semester or a 6-week, 8-week, or 10-week course. The book is filled with...



ALS Microsoft Windows XP Professional (Microsoft Press Academic Learn)
by Microsoft Press



The Women
by Hilton Als

A New York Times Notable BookDaring and fiercely original, The Women is at once a memoir, a psychological study, a sociopolitical manifesto, and an incisive adventure in literary criticism. It is conceived as a series of portraits analyzing the role that sexual and racial identity played in the lives and work of the writer's subjects: his mother, a self-described "Negress," who would not be...



ALS for the BLS Provider Field Guide
by American Academy of Orthopaedic Surgeons (AAOS), Daniel E. Glick, Art Breault

The ALS for the BLS Provider Field Guide is a tool that allows first responders and EMT-Basics to provide quality assistance to their ALS counterparts. The guide is a ready review of the most critical skills that BLS providers may be asked to assist with in the field. This durable, water-resistant field guide features bulleted text and illustrations that guide BLS personnel through critical...



ALS Security+ Certification Package (Microsoft Official Academic Course Series)
by Microsoft Official Academic Course

A complete program of textbook, lab manual, and software, this Academic Learning Series textbook and lab manual provides everything students need to build the knowledge and skills necessary to implement and manage network security. Coverage includes authentication, encryption, public key infrastructure, and network infrastructure. In addition, this textbook will help students to prepare for the...



Als-Lou Gehrig's Disease (Diseases and People)
by Mary Dodson Wade



ALS Case Studies in Emergency Care
by Edward V. Dickinson, Andrew Stern

This case-based resource provides real-world application of advanced life support techniques. This is an ideal book for both original and refresher Advanced Life Support training, or as a resource for the experience provider. It details the techniques necessary in advance life support while highlighting cases that allow for real-world application of this essential information. For advanced...



Langenscheidt Großwörterbuch Deutsch als Fremdsprache
by unknown



I Choose to Live: A Journey Through Life with ALS
by William Sinton

© 2008 BrightSurf.com