TY - JOUR
T1 - Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment
AU - Colicino, Elena
AU - Power, Melinda C.
AU - Cox, David G.
AU - Weisskopf, Marc G.
AU - Hou, Lifang
AU - Alexeeff, Stacy E.
AU - Sanchez-Guerra, Marco
AU - Vokonas, Pantel
AU - Spiro, Avron
AU - Schwartz, Joel
AU - Baccarelli, Andrea A.
N1 - Funding Information:
EC is supported by a grant from the National Institute of Environmental Health Sciences (NIEHS) (R01ES021733). Other support comes from NIEHS grants ES015172, ES014663 and ES020010, and Environmental Protection Agency (EPA) grant RD832416. The US Department of Veterans Affairs (VA) Normative Aging Study (NAS) is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Cognitive data collection at the VA NAS was supported by a VA Merit Review and a CSR&D Research Career Scientist award to AS. The views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. Additional support was provided by the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510). MCP was supported by grants from the NIEHS (T32 ES007069) and National Institute of Aging (NIA) (F31 AG038233).
Publisher Copyright:
© 2014 Colicino et al.; licensee BioMed Central Ltd.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Air pollution
KW - Black carbon
KW - Cognitive decline
KW - Mini-mental state examination
KW - mtDNA haplogroups
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U2 - 10.1186/1476-069X-13-42
DO - 10.1186/1476-069X-13-42
M3 - Article
C2 - 24884505
AN - SCOPUS:84988694103
SN - 1476-069X
VL - 13
JO - Environmental Health: A Global Access Science Source
JF - Environmental Health: A Global Access Science Source
IS - 1
M1 - 42
ER -