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

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 Northwester DNA study samples were not analysed 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.

Source: EurekAlert.
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