Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function

Ki Do Eum; Florence T. Wang; Joel Schwartz; Craig P. Hersh; Karl Kelsey; Robert O. Wright; Avron Spiro; David Sparrow; Howard Hu; Marc G. Weisskopf

doi:10.1016/j.neuro.2013.08.002

Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function

Ki Do Eum, Florence T. Wang, Joel Schwartz, Craig P. Hersh, Karl Kelsey, Robert O. Wright, Avron Spiro, David Sparrow, Howard Hu, Marc G. Weisskopf

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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 15. μg/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.

Original language	English
Pages (from-to)	65-71
Number of pages	7
Journal	NeuroToxicology
Volume	39
DOIs	https://doi.org/10.1016/j.neuro.2013.08.002
State	Published - Dec 2013

Keywords

Cognitive function
Environmental exposure
Gene-environment interaction
Glutathione S-transferase
Lead

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@article{45d9232fd0b841369cf327089043f3c3,

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 15. μg/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.",

keywords = "Cognitive function, Environmental exposure, Gene-environment interaction, Glutathione S-transferase, Lead",

author = "Eum, {Ki Do} and Wang, {Florence T.} and Joel Schwartz and Hersh, {Craig P.} and Karl Kelsey and Wright, {Robert O.} and Avron Spiro and David Sparrow and Howard Hu and Weisskopf, {Marc G.}",

note = "Funding Information: This work was supported by grants 5-P42-ES05947 , R01-ES05257 , and ES-00002 from the National Institutes of Health . F. Wang was partially supported by National Institute for Occupational Safety and Health (NIOSH) Grant T42/CCT110421 and T32 ES007155 from the National Institutes of Health . Funding Information: The Cognition and Health in Aging Men Project (CHAMP) has been supported by the Research Services of the US Department of Veterans Affairs, the National Institutes of Health (grants R01-AA08941 , R01-AG13006 , R01-AG14345 , R01-AG18436 ), the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510), and VA Merit Review and Research Career Scientist awards from VA Clinical Science Research and Development Service. Funding Information: The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). This research was also supported by a VA Merit Review and a VA Research Career Scientist award to D. Sparrow. ",

year = "2013",

month = dec,

doi = "10.1016/j.neuro.2013.08.002",

language = "English",

volume = "39",

pages = "65--71",

journal = "NeuroToxicology",

issn = "0161-813X",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function

AU - Eum, Ki Do

AU - Wang, Florence T.

AU - Schwartz, Joel

AU - Hersh, Craig P.

AU - Kelsey, Karl

AU - Wright, Robert O.

AU - Spiro, Avron

AU - Sparrow, David

AU - Hu, Howard

AU - Weisskopf, Marc G.

N1 - Funding Information: This work was supported by grants 5-P42-ES05947 , R01-ES05257 , and ES-00002 from the National Institutes of Health . F. Wang was partially supported by National Institute for Occupational Safety and Health (NIOSH) Grant T42/CCT110421 and T32 ES007155 from the National Institutes of Health . Funding Information: The Cognition and Health in Aging Men Project (CHAMP) has been supported by the Research Services of the US Department of Veterans Affairs, the National Institutes of Health (grants R01-AA08941 , R01-AG13006 , R01-AG14345 , R01-AG18436 ), the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510), and VA Merit Review and Research Career Scientist awards from VA Clinical Science Research and Development Service. Funding Information: The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). This research was also supported by a VA Merit Review and a VA Research Career Scientist award to D. Sparrow.

PY - 2013/12

Y1 - 2013/12

N2 - 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 15. μg/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.

AB - 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 15. μg/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.

KW - Cognitive function

KW - Environmental exposure

KW - Gene-environment interaction

KW - Glutathione S-transferase

KW - Lead

UR - http://www.scopus.com/inward/record.url?scp=84883773201&partnerID=8YFLogxK

U2 - 10.1016/j.neuro.2013.08.002

DO - 10.1016/j.neuro.2013.08.002

M3 - Article

C2 - 23958642

AN - SCOPUS:84883773201

SN - 0161-813X

VL - 39

SP - 65

EP - 71

JO - NeuroToxicology

JF - NeuroToxicology

ER -

Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function

Abstract

Keywords

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