4.7 Article

Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment

Journal

ENVIRONMENTAL HEALTH
Volume 13, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/1476-069X-13-42

Keywords

mtDNA haplogroups; Air pollution; Black carbon; Cognitive decline; Mini-mental state examination

Funding

  1. National Institute of Environmental Health Sciences (NIEHS) [R01ES021733]
  2. NIEHS [ES015172, ES014663, ES020010, T32 ES007069]
  3. Environmental Protection Agency (EPA) [RD832416]
  4. Cooperative Studies Program/ERIC, US Department of Veterans Affairs
  5. VA Merit Review
  6. CSR&D Research Career Scientist award
  7. US Department of Agriculture, Agricultural Research Service [53-K06-510]
  8. National Institute of Aging (NIA) [F31 AG038233]

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Background: Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods: We investigated 582 older men (72 +/- 7 years) in the VA Normative Aging Study cohort with = 4 visits per participant (1.8 in average) between 1995-2007. Low (<= 25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant's address. Results: Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions: The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects.

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