Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD.
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.
Budulac
Simona E
SE
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Postma
Dirkje S
DS
Hiemstra
Pieter S
PS
Kunz
Lisette I Z
LI
Siedlinski
Mateusz
M
Smit
Henriette A
HA
Vonk
Judith M
JM
Rutgers
Bea
B
Timens
Wim
W
Boezen
H Marike
HM
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
D015415:Biomarkers; D018836:Inflammation Mediators; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1