title: Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function.
abstract: BACKGROUND
  Glutathione-S-transferase gene (GST) polymorphisms can result in variable ability of these enzymes to remove electrophilic substrates. We investigated whether the GSTP1 Val105 and GSTM1 deletion polymorphisms modify the lead-cognitive function association.
  
  
  METHODS
  We used repeated measures analysis to compare the association between cumulative lead biomarkers-bone lead measured using K-shell X-Ray Fluorescence-and Mini-Mental State Exam (MMSE) score by GST variants, adjusted for covariates, among Normative Aging Study participants, a Boston-based prospective cohort of men. We had complete data for 698 men (providing 1292 observations) for GSTM1 analyses and 595 men (providing 1142 observations) for GSTP1 analyses.
  
  
  RESULTS
  A 15μg/g higher tibia lead concentration (interquartile range of tibia lead) was associated with a 0.24 point decrement in MMSE score among GSTP1 Val105 variant carriers, which was significantly stronger than the association among men with only wild-type alleles (p=0.01). The association among GSTP1 Val105 carriers was comparable to that of 3 years of age in baseline MMSE scores. The association between tibia lead and MMSE score appeared progressively steeper in participants with increasingly more GSTP1 Val105 alleles. A modest association between tibia lead and lower MMSE score was seen among participants with the GSTM1 deletion polymorphism. Neither of the glutathione S-transferase variants was independently associated with cognitive function, nor with lead biomarker measures. The results pertaining to patella lead were similar to those observed for tibia lead.
  
  
  CONCLUSIONS
  Our results suggest that the GSTP1 Val105 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure.
authors: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors: Ki-Do
authors: KD
authors: Eum
authors: Florence T
authors: FT
authors: Wang
authors: Joel
authors: J
authors: Schwartz
authors: Craig P
authors: CP
authors: Hersh
authors: Karl
authors: K
authors: Kelsey
authors: Robert O
authors: RO
authors: Wright
authors: Avron
authors: A
authors: Spiro
authors: David
authors: D
authors: Sparrow
authors: Howard
authors: H
authors: Hu
authors: Marc G
authors: MG
authors: Weisskopf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007854:Lead / Q000032:analysis* / Q000097:blood; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D013052:Spectrometry, X-Ray Emission; D014633:Valine / Q000235:genetics; D014728:Veterans
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007854:Lead; D014633:Valine; C496556:GSTP1 protein, human
keywords: Cognitive function; Environmental exposure; Gene–environment interaction; Glutathione S-transferase; Lead
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