Background: Recent observational studies have linked traffic-related air pollution to loss of cognitive function in the elderly, an effect potentially mediated by oxidative-stress actions on the brain. Mitochondria are the main cellular source of oxidative stress. Haplogroups in mitochondrial DNA (mtDNA) determine between-subject differences in oxidative potential and have been linked with neurodegerative disease. No study has yet investigated whether mtDNA haplogroups influence susceptibility to pro-oxidant exposures, including traffic-related pollution. Aims: To investigate whether mtDNA haplogroups determine differential susceptibility to the effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution, on cognitive function in older men. Methods: A cohort of 616 men (mean±SD, 71±7 years of age) with an average 1.8 visits (from 1 to 4) per participant between 1996-2007 was drawn from the VA Normative Aging Study. We focused on low (＜25) Mini Mental State Examination (MMSE) score as proxy of impaired cognition in multiple domains. We fitted repeated-measure logistic regression using BC estimated at participant's address in the year before the first visit through a validated spatio-temporal land-use regression model. Results: In models adjusted for clinical features and socio-economics factors, each doubling in BC was associated with 1.2 (95%CI 0.9-1.5) times higher odds of low MMSE score. BC effect on MMSE differed by hapiogroup, with most of the effect found in carriers of haplogroups I (OR=3.4; 95%CI 0.8-13.7) or X (OR=2.3; 95%CI 0.9-5.5). Carriers of haplotypes J, T, H V, K, U and W did not show any effect from BC. Conclusions: Susceptibility to the adverse cognitive effects of BC was limited to carriers of mtDNA haplogroups I and X. mtDNA haplogroups may represent a novel susceptibility factor that, due to the central role of oxidative stress in mediating air pollution risks, may also modify effects on other systems.
展开▼
