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

Elena Colicino*, Melinda C. Power, David G. Cox, Marc G. Weisskopf, Lifang Hou, Stacy E. Alexeeff, Marco Sanchez-Guerra, Pantel Vokonas, Avron Spiro, Joel Schwartz, Andrea A. Baccarelli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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 le;4 visits per participant (1.8 in average) between 1995-2007. Low (le;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.

Original languageEnglish (US)
Article number42
JournalEnvironmental Health: A Global Access Science Source
Volume13
Issue number1
DOIs
StatePublished - 2014

Keywords

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

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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