Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline.
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| Title: | Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline. |
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| Authors: | Wang, Florence T.1 Florence.Wang@i3drugsafety.com, Hu, Howard1,2,3, Schwartz, Joel1,4, Weuve, Jennifer1, Spiro III, Avron S.5,6, Sparrow, David5,7, Huiling Nie1,3, Silverman, Edwin K.3, Weiss, Scott T.1,3, Wright, Robert O.1,3,8 |
| Source: | Environmental Health Perspectives. May2007, Vol. 115 Issue 5, p1-33. 33p. |
| Subject Terms: | *Lead toxicology, Cognitive testing, Biological neural networks, Diseases in older people, Fibrinogen polymorphisms, Tibia, Patella |
| Abstract: | Background: As iron and lead promote oxidative damage, and HFE gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship. Objective: To assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults. Methods: Tibia and patella lead were measured using K-x-ray fluorescence (1991-1999) among participants of the Normative Aging Study, a longitudinal study of community-dwelling men from greater Boston. We assessed cognitive function with the Mini-Mental State Examination (MMSE) twice (1993-1998 and 1995-2000) and genotyped participants for HFE polymorphisms. We estimated the adjusted mean differences in lead-associated annual cognitive decline across HFE genotype groups (n=358). Results: Higher tibia lead was associated with steeper cognitive decline among participants with at least one HFE variant allele as compared to men with only wildtype alleles (pinteraction=0.03), such that a 15 µg/g increase in tibia lead was associated with a 0.2 point annual decrement in MMSE score among HFE variant allele carriers. This difference in scores among men with at least one variant allele was comparable to the difference in baseline MMSE scores that we observed among men who were 4 years apart in age. Moreover, the deleterious association between tibia lead and cognitive decline appeared progressively worse in participants with increasingly more copies of HFE variant alleles (ptrend=0.008). Results pertaining to patella lead were similar. Conclusion: Our findings suggest that HFE polymorphisms greatly enhance susceptibility to lead-related cognitive impairment in a pattern consistent with allelelic dose. [ABSTRACT FROM AUTHOR] |
| Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | GreenFILE |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: 8gh DbLabel: GreenFILE An: 25744097 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Wang%2C+Florence+T%2E%22">Wang, Florence T.</searchLink><relatesTo>1</relatesTo><i> Florence.Wang@i3drugsafety.com</i><br /><searchLink fieldCode="AR" term="%22Hu%2C+Howard%22">Hu, Howard</searchLink><relatesTo>1,2,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Schwartz%2C+Joel%22">Schwartz, Joel</searchLink><relatesTo>1,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Weuve%2C+Jennifer%22">Weuve, Jennifer</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Spiro+III%2C+Avron+S%2E%22">Spiro III, Avron S.</searchLink><relatesTo>5,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Sparrow%2C+David%22">Sparrow, David</searchLink><relatesTo>5,7</relatesTo><br /><searchLink fieldCode="AR" term="%22Huiling+Nie%22">Huiling Nie</searchLink><relatesTo>1,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Silverman%2C+Edwin+K%2E%22">Silverman, Edwin K.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Weiss%2C+Scott+T%2E%22">Weiss, Scott T.</searchLink><relatesTo>1,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Wright%2C+Robert+O%2E%22">Wright, Robert O.</searchLink><relatesTo>1,3,8</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. May2007, Vol. 115 Issue 5, p1-33. 33p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22Lead+toxicology%22">Lead toxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Cognitive+testing%22">Cognitive testing</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+neural+networks%22">Biological neural networks</searchLink><br /><searchLink fieldCode="DE" term="%22Diseases+in+older+people%22">Diseases in older people</searchLink><br /><searchLink fieldCode="DE" term="%22Fibrinogen+polymorphisms%22">Fibrinogen polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Tibia%22">Tibia</searchLink><br /><searchLink fieldCode="DE" term="%22Patella%22">Patella</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: As iron and lead promote oxidative damage, and HFE gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship. Objective: To assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults. Methods: Tibia and patella lead were measured using K-x-ray fluorescence (1991-1999) among participants of the Normative Aging Study, a longitudinal study of community-dwelling men from greater Boston. We assessed cognitive function with the Mini-Mental State Examination (MMSE) twice (1993-1998 and 1995-2000) and genotyped participants for HFE polymorphisms. We estimated the adjusted mean differences in lead-associated annual cognitive decline across HFE genotype groups (n=358). Results: Higher tibia lead was associated with steeper cognitive decline among participants with at least one HFE variant allele as compared to men with only wildtype alleles (pinteraction=0.03), such that a 15 µg/g increase in tibia lead was associated with a 0.2 point annual decrement in MMSE score among HFE variant allele carriers. This difference in scores among men with at least one variant allele was comparable to the difference in baseline MMSE scores that we observed among men who were 4 years apart in age. Moreover, the deleterious association between tibia lead and cognitive decline appeared progressively worse in participants with increasingly more copies of HFE variant alleles (ptrend=0.008). Results pertaining to patella lead were similar. Conclusion: Our findings suggest that HFE polymorphisms greatly enhance susceptibility to lead-related cognitive impairment in a pattern consistent with allelelic dose. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 33 StartPage: 1 Subjects: – SubjectFull: Lead toxicology Type: general – SubjectFull: Cognitive testing Type: general – SubjectFull: Biological neural networks Type: general – SubjectFull: Diseases in older people Type: general – SubjectFull: Fibrinogen polymorphisms Type: general – SubjectFull: Tibia Type: general – SubjectFull: Patella Type: general Titles: – TitleFull: Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Wang, Florence T. – PersonEntity: Name: NameFull: Hu, Howard – PersonEntity: Name: NameFull: Schwartz, Joel – PersonEntity: Name: NameFull: Weuve, Jennifer – PersonEntity: Name: NameFull: Spiro III, Avron S. – PersonEntity: Name: NameFull: Sparrow, David – PersonEntity: Name: NameFull: Huiling Nie – PersonEntity: Name: NameFull: Silverman, Edwin K. – PersonEntity: Name: NameFull: Weiss, Scott T. – PersonEntity: Name: NameFull: Wright, Robert O. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: May2007 Type: published Y: 2007 Identifiers: – Type: issn-print Value: 00916765 Numbering: – Type: volume Value: 115 – Type: issue Value: 5 Titles: – TitleFull: Environmental Health Perspectives Type: main |
| ResultId | 1 |
