Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson’s disease

Abstract

GSTs are a family of inducible phase II enzymes that may play a neuroprotective role in Parkinson’s
disease (PD). GSTs may also modify PD risk by metabolizing compounds in cigarettes, as cigarette
smoking is generally found to be associated with a decrease in PD risk. Using a population-based
case control study design, we examined polymorphisms of the mu, omega, pi, and theta classes of
GST to elucidate the main effects and smoking-GST interactions on PD risk. From three rural
California counties, we recruited 289 incident idiopathic PD cases, clinically confirmed by our study
neurologist, and 270 population controls, marginally matched by age, gender, and race.
We assessed main gene polymorphism associations and evaluated interactions between smoking and
GST polymorphisms as departures from a multiplicative scale adjusting for age, gender, and race.
We also restricted analyses to Caucasian subjects to address the potential for population stratification
(n=235 cases, 220 controls).
Among Caucasians, we observed a risk reduction in subjects carrying at least one variant allele for
GSTO1 (OR= 0.68, 95% CI: 0.47–0.98) and also GSTO2 (OR= 0.64, 95% CI: 0.44–0.93); both genes
were in strong linkage disequilibrium. No main gene effects were observed for the remaining
polymorphisms. We noted a multiplicative interaction between ever having smoked regularly and
GSTO1 (ORinteraction= 0.55, 95% CI: 0.33–0.92) and GSTO2 (ORinteraction= 0.54, 95% CI: 0.32–
0.90). Results were similar when combining all races. These findings and the paucity of similar
studies suggests a need for further inquiry into the association between GSTs, smoking, and PD risk.