Glutathione S-transferase polymorphisms and onset age in α-synuclein A53T mutant Parkinson's disease

Lawrence I. Golbe, Giuseppe Di Iorio, Katerina Markopoulou, Aglaia Athanassiadou, Spiridon Papapetropoulos, Ray L. Watts, Jeffery M. Vance, Vincenzo Bonifati, Tanishia A. Williams, John R. Spychala, E. Scot Stenroos, Williams G. Johnson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)254-258
Number of pages5
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume144
Issue number2
DOIs
StatePublished - Mar 5 2007
Externally publishedYes

Keywords

  • Contursi kindred
  • Detoxification
  • Glutathione
  • GST-P1
  • PARK-1

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

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