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

Environmental Health

Research

Elena Colicino¹  Stacy E Alexeeff¹  Marco Sanchez-Guerra¹  Melinda C Power²  Andrea A Baccarelli²  Joel Schwartz²  Marc G Weisskopf²  Lifang Hou³  David G Cox⁴  Avron Spiro III⁵  Pantel Vokonas⁵ 

[1] Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave, 02115, Boston, MA, USA;Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave, 02115, Boston, MA, USA;Department of Epidemiology, Harvard School of Public Health, 665 Huntington Ave, 02115, Boston, MA, USA;Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 420 East Superior St, 60611, Chicago, IL, USA;INSERM U1052, Centre de Recherche en Cancérologie de Lyon, F-69000, Lyon, France;Centre Léon Bérard, Pole de Recherche Translationnelle, F-69008, Lyon, France;VA Boston Healthcare System, Boston University Schools of Public Health and Medicine, 88E Newton St, 02118, Boston, MA, USA;

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

DOI  :  10.1186/1476-069X-13-42

 received in 2014-02-12, accepted in 2014-05-02,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundTraffic-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.MethodsWe 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.ResultsMitochondrial 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Colicino et al.; licensee BioMed Central Ltd. 2014