Further evidence for an association of the paraoxonase 1 (PON1) Met-54 allele with Parkinson's disease

Mov Disord. 2002 Jul;17(4):764-6. doi: 10.1002/mds.10172.

Abstract

Paraoxonase1 (PON1) is an arylesterase mainly expressed in the liver that hydrolyzes organophosphates such as pesticides, reported risk factors for Parkinson's disease (PD), and other neurotoxins. A Leu-Met 54 polymorphism in the gene for PON1-affecting enzyme activity was recently shown, employing a new restriction enzyme technique, to be associated with Parkinson's disease. We examined the same polymorphism by automated capillary sequencing in a sample of Caucasian subjects from the Stockholm area in Sweden (127 healthy individuals and 114 patients with PD) and found similar distributions and a similar difference in our sample. The genotype distribution in our PD material was LL 36.0%, LM 45.6%, and MM 18.4%; in our control material, it was LL 45.7%, LM 44.1%, and MM 10.2%. Based on the previously established increase in allele frequencies of the lower-activity Met-variant of PON1, we could confirm a significant association using a one-sided chi(2) test. Results remained significant with a two-sided chi(2) test, allowing for both increases and decreases in frequencies. Our data confirm an association between the PON1 Leu-Met 54 polymorphism and PD by demonstrating a similar association. The distribution between familial and nonfamilial PD patients was equal. No other synonymous or nonsynonymous polymorphisms were found in the sequenced coding region of PON1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles*
  • Amino Acid Substitution / genetics
  • Aryldialkylphosphatase
  • Esterases / genetics*
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Leucine / genetics*
  • Lipid Peroxidation / genetics
  • Male
  • Methionine / genetics*
  • Middle Aged
  • Parkinson Disease / diagnosis
  • Parkinson Disease / genetics*
  • Polymorphism, Genetic / genetics*
  • Reference Values
  • Sweden

Substances

  • Methionine
  • Esterases
  • Aryldialkylphosphatase
  • PON1 protein, human
  • Leucine