title: Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment.
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 ≤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.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA. ecolicin@hsph.harvard.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.forename: Melinda C
authors.initials: MC
authors.lastname: Power
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Stacy E
authors.initials: SE
authors.lastname: Alexeeff
authors.forename: Marco
authors.initials: M
authors.lastname: Sanchez-Guerra
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Avron
authors.initials: A
authors.lastname: Spiro
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D053260:Soot / Q000032:analysis / Q000633:toxicity*; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D004272:DNA, Mitochondrial; D053260:Soot; D001335:Vehicle Emissions