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


Show simple item record Wang, Florence T. en_US Hu, Howard en_US Schwartz, Joel en_US Weuve, Jennifer en_US Spiro, Avron S. en_US Sparrow, David en_US Nie, Huiling en_US Silverman, Edwin K. en_US Weiss, Scott T. en_US Wright, Robert O. en_US 2012-01-09T14:19:06Z 2012-01-09T14:19:06Z 2007-08 en_US
dc.identifier.citation Wang, Florence T., Howard Hu, Joel Schwartz, Jennifer Weuve, Avron S. Spiro, David Sparrow, Huiling Nie, Edwin K. Silverman, Scott T. Weiss, Robert O. Wright. "Modifying Effects of the HFE Polymorphisms on the Association Between Lead Burden and Cognitive Decline" Environmental Health Perspectives 115(8): 1210-1215. (2007) en_US
dc.description.abstract BACKGROUND. As iron and lead promote oxidative damage, and hemochromatosis (HFE) gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship. OBJECTIVE. Our goal was to assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults. METHODS. We measured tibia and patella lead 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 compared with men with only wild-type alleles (p interaction = 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 (p-trend = 0.008). Results for 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. en_US
dc.description.sponsorship Cognition and Health in Aging Men Project; VA Normative Aging Study; United States Deparment of Veterans Affairs; National Institutes of Health (AA08941, AG13006, AG14345, AG18436, ES05947, ES05257, CCT110421, ES007155); United States Department of Agriculture (53-K06-510); Massachusetts Veterans Epidemiology Research and Information Center en_US
dc.language.iso en en_US
dc.publisher National Institute of Environmental Health Sciences en_US
dc.subject Cognitive decline en_US
dc.subject Epidemiology en_US
dc.subject HFE en_US
dc.subject Lead en_US
dc.subject Longitudinal studies en_US
dc.subject Neuropsychologic tests en_US
dc.title Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline en_US
dc.type article en_US
dc.identifier.doi 10.1289/ehp.9855 en_US
dc.identifier.pubmedid 17687449 en_US
dc.identifier.pmcid 1940090 en_US

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