Glutathione S-transferase polymorphisms and onset age in alpha-synuclein A53T mutant Parkinson's disease.
Monogenic forms of Parkinson's disease (PD) provide an opportunity to examine mechanisms underlying phenotypic variation. Glutathione S-transferase (GST) has detoxification and antioxidative functions. To screen genetic variations in GST for an effect on the onset age (OA) of PD, we typed seven common genetic polymorphisms in five GST isoenzymes, M1, M3, P1, T1, and Z1, in 36 affected individuals of Italian or Greek origin with the alpha-synuclein A53T (PARK1) mutation. Mean OA was 45.2 years with a wide SD of 11.03 years, similar to that of idiopathic PD. Our allelic analysis showed that the subjects homozygous for the GSTP1 G-for-A nucleotide substitution at position 313 had a mean OA acceleration of 15.2 years (31.3 +/- 7.09 years, n = 3 vs. 46.5 +/- 10.50 years, n = 33, P = 0.020). The GSTP1 C341T substitution was associated with a 9.7-year acceleration of OA, but the significance was borderline (36.4 +/- 8.35 years vs. 46.7 +/- 10.85 years, P = 0.0519). After correction for the five genes examined, both results lose statistical significance. Nevertheless, our results suggest that further investigation in GSTP1 variants and PD pathogenesis is warranted in sporadic PD and that a search for toxins that accelerate PD OA should pay particular attention to GST-P1 substrates.
Golbe
Lawrence I
LI
Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. golbe@umdnj.edu
Di Iorio
Giuseppe
G
Markopoulou
Katerina
K
Athanassiadou
Aglaia
A
Papapetropoulos
Spiridon
S
Watts
Ray L
RL
Vance
Jeffery M
JM
Bonifati
Vincenzo
V
Williams
Tanishia A
TA
Spychala
John R
JR
Stenroos
E Scot
ES
Johnson
Williams G
WG
D000225:Adenine; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D013941:Thymine; D051844:alpha-Synuclein / Q000235:genetics*
D050505:Mutant Proteins; D051844:alpha-Synuclein; D005982:Glutathione Transferase; D000225:Adenine; D013941:Thymine