title: Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD.
abstract: BACKGROUND
  Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV1 in two independent population based cohorts. The aim of our study was to assess the associations of MRP1 SNPs with FEV1 level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.
  
  
  METHODS
  Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients. The effects of MRP1 SNPs were analyzed using linear regression models.
  
  
  RESULTS
  One SNP, rs212093 was significantly associated with a higher FEV1 level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV1 level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.
  
  
  CONCLUSIONS
  This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies.
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Simona E
authors.initials: SE
authors.lastname: Budulac
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: Lisette I Z
authors.initials: LI
authors.lastname: Kunz
authors.forename: Mateusz
authors.initials: M
authors.lastname: Siedlinski
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Smit
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.forename: Bea
authors.initials: B
authors.lastname: Rutgers
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001980:Bronchi / Q000737:chemistry* / Q000276:immunology / Q000503:physiopathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000097:blood* / Q000235:genetics*; D009426:Netherlands; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013183:Sputum / Q000276:immunology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1