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Interaction between PON1 and population density in amyotrophic lateral sclerosis

Diekstra, Frank P.; Beleza-Meireles, Ana; Leigh, Nigel P.; Shaw, Christopher E.; Al-Chalabi, Ammar

doi: 10.1097/WNR.0b013e32831af220
Genetics of Nervous System Diseases

Paraoxonase polymorphisms have been associated with amyotrophic lateral sclerosis (ALS). Paraoxonases are detoxifying enzymes involved in the metabolism of organophosphates. We tested the hypothesis that genetic variation within paraoxonase genes would interact with the environmental exposure to paraoxonase substrates. We used population density in the location of residence of ALS patients as a surrogate marker for environmental exposure. Paraoxonase genotypes at previously associated single nucleotide polymorphisms rs662, rs854560, rs6954345, and rs11981433 were studied in 98 patients from the South East England ALS population-based register. A case-only analysis was carried out and median population density was used to categorize patients into rural or urban environments. We found a significant interaction with population density for marker rs854560 (L55M) in ALS.

MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London, UK

Correspondence to Professor Ammar Al-Chalabi, PhD, FRCP, MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, P 043, London SE5 8AF, UK

Tel: +44 20 7848 5172; fax: +44 20 7848 5190; e-mail: ammar@iop.kcl.ac.uk

Received 22 August 2008; accepted 24 September 2008

© 2009 Lippincott Williams & Wilkins, Inc.