Open Access Research

Modification by hemochromatosis gene polymorphisms of the association between traffic-related air pollution and cognition in older men: a cohort study

Melinda C Power12*, Marc G Weisskopf12, Stacey E Alexeeff3, Robert O Wright2, Brent A Coull3, Avron Spiro456 and Joel Schwartz12

Author Affiliations

1 Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA

2 Department of Environmental Health, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA

3 Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

4 Veterans Affairs Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA, 02130, USA

5 Department of Epidemiology, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, USA

6 Department of Psychiatry, Boston University Medical School, 72 East Concord Street, Boston, MA, 02118, USA

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Environmental Health 2013, 12:16  doi:10.1186/1476-069X-12-16

Published: 15 February 2013

Abstract

Background

Previous studies found effect modification of associations between traffic-related air pollution and cardiovascular outcomes by polymorphisms in the hemochromatosis gene (HFE). As traffic-related air pollution may impact cognition through effects on cardiovascular health or through mechanisms which may also influence cardiovascular outcomes, we hypothesized that HFE polymorphisms would also modify a previously observed association between traffic-related air pollution exposure and cognition in older men.

Methods

We considered data from 628 participants of the VA Normative Aging Study. We estimated long term exposure to black carbon (BC), a marker of traffic related air pollution, using a spatio-temporal land use regression model. We assessed cognition using the Mini-Mental State Examination (MMSE), a test of global function, and performance on a battery of other tests, covering a wide range of domains. We investigated whether variants of HFE C282Y and H63D modified the association between BC and having a low MMSE score using logistic models with generalized estimating equations and multiplicative interaction terms. Similarly, we assessed whether HFE variants modified the association between BC and performance on the cognitive battery using linear mixed models with multiplicative interaction terms.

Results

Our results suggest modification of the BC-cognition association by HFE C282Y, although the test of interaction did not achieve statistical significance. In multivariable-adjusted models, participants who lacked a HFE C282Y variant (CC) exhibited an adverse association between BC and total cognition z-score (beta for a doubling in BC concentration: -0.061, 95% CI: -0.115, -0.007), while we did not observe an association in participants with at least one variant genotype (CY or YY) (beta for a doubling in BC concentration: 0.073, 95% CI: -0.081, 0.228; p-value for interaction: 0.11). The pattern of association was similar for analyses considering performance on the Mini-Mental State Examination. There was little evidence to support effect modification of the BC-cognition association by the HFE H63D genotype.

Conclusions

Our data suggest that older adults who lack an HFE C282Y variant may be more susceptible to an adverse effect of traffic-related air pollution exposure on cognition. This finding and the proposed biological mechanism require confirmation.

Keywords:
Aging; Black carbon; Cognitive dysfunction; Epidemiology; Particulate matter; HFE; Hemochromatosis; Gene-environment interaction; Susceptible group