Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease.
Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p=0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD.
Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden. Andrea.Carmine.Belin@ki.se
Andrea Carmine
AC
Belin
Caroline
C
Ran
Anna
A
Anvret
Silvia
S
Paddock
Marie
M
Westerlund
Anna
A
Håkansson
Hans
H
Nissbrandt
Peter
P
Söderkvist
Nil
N
Dizdar
Ahmad
A
Ahmadi
Maria
M
Anvret
Thomas
T
Willows
Olof
O
Sydow
Dagmar
D
Galter
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human