title: Black carbon exposures, blood pressure, and interactions with single nucleotide polymorphisms in MicroRNA processing genes.
abstract: BACKGROUND
  Black carbon (BC) is a marker of traffic pollution that has been associated with blood pressure (BP), but findings have been inconsistent. MicroRNAs (miRNAs) are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of miRNAs to maturity influence susceptibility to BC has not been elucidated.
  
  
  OBJECTIVE
  We investigated the association between BC and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in miRNA processing genes.
  
  
  METHODS
  Repeated measures analyses were performed using data from the VA Normative Aging Study. Complete covariate data were available for 789 participants with one to six study visits between 1995 and 2008. In models of systolic and diastolic BP, we examined SNP-by-BC interactions with 19 miRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle, and meteorologic factors.
  
  
  RESULTS
  A 1-SD increase in BC (0.415 microg/m(3)) was associated with 3.04 mmHg higher systolic (95% confidence interval (CI), 2.29-3.79) and 2.28 mmHg higher diastolic BP (95% CI, 1.88-2.67). Interactions modifying BC associations were observed with SNPs in the DICER, GEMIN4, and DiGeorge critical region-8 (DGCR8) genes, and in GEMIN3 and GEMIN4, predicting diastolic and systolic BP, respectively.
  
  
  CONCLUSIONS
  We observed evidence of effect modification of the association between BP and 7-day BC moving averages by SNPs associated with miRNA processing. Although the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing BC effects.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA. ewilker@bidmc.harvard.edu
authors.forename: Elissa H
authors.initials: EH
authors.lastname: Wilker
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Helen
authors.initials: H
authors.lastname: Suh
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects*; D002244:Carbon / Q000737:chemistry; D053487:DEAD-box RNA Helicases / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005808:Genes, Recessive / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008404:Massachusetts; D035683:MicroRNAs / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics
chemical_list: D000393:Air Pollutants; C474043:DGCR8 protein, human; C406815:GEMIN4 protein, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D052638:Particulate Matter; D011506:Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D002244:Carbon; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases