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.
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.
Authors: José A G Agúndez; Antonio Luengo; Oscar Herráez; Carmen Martínez; Hortensia Alonso-Navarro; Félix Javier Jiménez-Jiménez; Elena García-Martín Journal: Neuromolecular Med Date: 2007-11-06 Impact factor: 3.843
Authors: Katja Zschiedrich; Inke R König; Norbert Brüggemann; Norman Kock; Meike Kasten; Klaus L Leenders; Vladimir Kostić; Peter Vieregge; Andreas Ziegler; Christine Klein; Katja Lohmann Journal: J Neurol Date: 2009-01-29 Impact factor: 4.849
Authors: Min Shi; Joshua Bradner; Theo K Bammler; David L Eaton; Jianpeng Zhang; ZuCheng Ye; Angela M Wilson; Thomas J Montine; Catherine Pan; Jing Zhang Journal: Am J Pathol Date: 2009-06-04 Impact factor: 4.307
Authors: Samuel M Goldman; Freya Kamel; G Webster Ross; Grace S Bhudhikanok; Jane A Hoppin; Monica Korell; Connie Marras; Cheryl Meng; David M Umbach; Meike Kasten; Anabel R Chade; Kathleen Comyns; Marie B Richards; Dale P Sandler; Aaron Blair; J William Langston; Caroline M Tanner Journal: Mov Disord Date: 2012-10-08 Impact factor: 10.338