Further evidence for an association of the paraoxonase 1 (PON1) Met-54 allele with Parkinson's disease.
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.
Carmine
Andrea
A
Department of Neuroscience, Retzius Laboratory, Karolinska Institutet, Stockholm, Sweden.
Buervenich
Silvia
S
Sydow
Olof
O
Anvret
Maria
M
Olson
Lars
L
D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D043303:Aryldialkylphosphatase; D004950:Esterases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007930:Leucine / Q000235:genetics*; D015227:Lipid Peroxidation / Q000235:genetics; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012016:Reference Values; D013548:Sweden
D008715:Methionine; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D007930:Leucine