Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age: the GenePD Study.
BACKGROUND
Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides.


METHODS
Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides. Haplotypes were similarly evaluated in stratified analyses.


RESULTS
Three SNPs were associated with PD onset age in the group of men occupationally exposed to herbicides. Three additional SNPs had significant trends for the association of PD onset age across the herbicide exposure groups. Haplotype results also provided evidence that the relation between GSTP1 and onset age is modified by herbicide exposure. One haplotype was associated with an approximately 8-years-earlier onset in the occupationally exposed group and a 2.8-years-later onset in the nonexposed group.


CONCLUSIONS
Herbicide exposure may be an effect modifier of the relation between glutathione S-transferase pi gene polymorphisms and onset age in familial PD.
Wilk
J B
JB
Department of Neurology, Boston University School of Medicine, 715 Albany St., E-338, Boston, MA 02118, USA. jwilk@bu.edu
Tobin
J E
JE
Suchowersky
O
O
Shill
H A
HA
Klein
C
C
Wooten
G F
GF
Lew
M F
MF
Mark
M H
MH
Guttman
M
M
Watts
R L
RL
Singer
C
C
Growdon
J H
JH
Latourelle
J C
JC
Saint-Hilaire
M H
MH
DeStefano
A L
AL
Prakash
R
R
Williamson
S
S
Berg
C J
CJ
Sun
M
M
Goldwurm
S
S
Pezzoli
G
G
Racette
B A
BA
Perlmutter
J S
JS
Parsian
A
A
Baker
K B
KB
Giroux
M L
ML
Litvan
I
I
Pramstaller
P P
PP
Nicholson
G
G
Burn
D J
DJ
Chinnery
P F
PF
Vieregge
P
P
Slevin
J T
JT
Cambi
F
F
MacDonald
M E
ME
Gusella
J F
JF
Myers
R H
RH
Golbe
L I
LI
D004198:Disease Susceptibility / Q000139:chemically induced; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006239:Haplotypes; D006540:Herbicides / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced* / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
D006540:Herbicides; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi