View in EDS PDF Full Text

Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline.

Saved in:
Bibliographic Details
Title: Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline.
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
Description
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]
ISSN:00916765