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Genetic Variations In Detoxifying Genes Lead To Lou Gehrig's diseases

A new study links the genetic variations in detoxifying enzymes for developing Lou Gehrig's diseases//.

The study shows that the genetic variations in three enzymes, which are used to detoxify insecticides and nerve gas agents as well as for metabolising cholesterol lowering, statin drugs might be a risk factor for developing irregular ‘Amyotrophic lateral sclerosis’ (ALS, or Lou Gehrig's disease). The study also indicates that this might be the possible cause for the reported two-fold increased risk of ALS in Gulf War veterans.

These findings, from a study led Teepu Siddique, M.D., and colleagues at North-western 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 North-western 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
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