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. CONCLUSION: Our results suggest that the GSTP1 Val105 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure.
BACKGROUND:Glutathione-S-transferase gene (GST) polymorphisms can result in variable ability of these enzymes to remove electrophilic substrates. We investigated whether the GSTP1Val105 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 GSTP1Val105 variant carriers, which was significantly stronger than the association among men with only wild-type alleles (p=0.01). The association among GSTP1Val105 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 GSTP1Val105 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. CONCLUSION: Our results suggest that the GSTP1Val105 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure.
Authors: David P Miller; Geoffrey Liu; Immaculata De Vivo; Thomas J Lynch; John C Wain; Li Su; David C Christiani Journal: Cancer Res Date: 2002-05-15 Impact factor: 12.701
Authors: R Soto-Otero; E Méndez-Alvarez; A Hermida-Ameijeiras; A M Muñoz-Patiño; J L Labandeira-Garcia Journal: J Neurochem Date: 2000-04 Impact factor: 5.372
Authors: D A Bennett; R S Wilson; J A Schneider; D A Evans; L A Beckett; N T Aggarwal; L L Barnes; J H Fox; J Bach Journal: Neurology Date: 2002-07-23 Impact factor: 9.910