title: Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women.
abstract: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases.
  
  
  
  Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population.
  
  
  
  Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM2.5and PM10exposures over 2-years were estimated for each participant's residential address using spatiotemporal interpolation in combination with a dispersion model.
  
  
  
  Average long-term PM10was 25.9 (± 5.4) and 23.7 (± 2.3) μg/m3in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM10and the expression of individual genes differed by sex. In the validation cohort, long-term PM10was associated with the expression ofDNAJB5andEAPPin men andARHGAP4(p= 0.053) in women.AKAP6andLIMK1were significantly associated with PM10in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM10exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00;p= 0.0002 in men, 0.86; 95% CI: 0.76, 0.96;p= 0.004 in women).
  
  
  
  Expression of the sex-specific candidate genes identified in the discovery population predicted PM10exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects.
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Vrijens
authors.forename: Ellen
authors.initials: E
authors.lastname: Winckelmans
authors.forename: Maria
authors.initials: M
authors.lastname: Tsamou
authors.forename: Willy
authors.initials: W
authors.lastname: Baeyens
authors.forename: Patrick
authors.initials: P
authors.lastname: De Boever
authors.forename: Danyel
authors.initials: D
authors.lastname: Jennen
authors.forename: Theo M
authors.initials: TM
authors.lastname: de Kok
authors.forename: Elly
authors.initials: E
authors.lastname: Den Hond
authors.forename: Wouter
authors.initials: W
authors.lastname: Lefebvre
authors.forename: Michelle
authors.initials: M
authors.lastname: Plusquin
authors.forename: Hans
authors.initials: H
authors.lastname: Reynders
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
authors.forename: Nicolas
authors.initials: N
authors.lastname: Van Larebeke
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vanpoucke
authors.forename: Jos
authors.initials: J
authors.lastname: Kleinjans
authors.forename: Tim S
authors.initials: TS
authors.lastname: Nawrot
mesh_terms: D000397:Air Pollution / Q000706:statistics & numerical data*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D052638:Particulate Matter; D012140:Respiratory Tract Diseases / Q000453:epidemiology; D012737:Sex Factors
chemical_list: D052638:Particulate Matter