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25,26 Furthermore, a polymorphism of the DHFR enzyme resulting in a 19bp deletion within the site of a key regulatory sequence has been theorized to exhibit negative effects on the expression and activity of this enzyme

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Cardiovascular or respiratory disease, renal or hepatic impairment, diabetes, Helicobacter pylori infection, rheumatoid arthritis, and hypertension are also associated with increased risk

These include, but are not limited to, genetic predisposition, neuroinflammation, head trauma, untreated hypertension, diabetes, Parkinsons disease, HIV infection and normal aging

PMID 15996001

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