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Published in: Respiratory Research 1/2010

Open Access 01-12-2010 | Research

Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD

Authors: Simona E Budulac, Dirkje S Postma, Pieter S Hiemstra, Lisette IZ Kunz, Mateusz Siedlinski, Henriette A Smit, Judith M Vonk, Bea Rutgers, Wim Timens, H Marike Boezen, the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study group

Published in: Respiratory Research | Issue 1/2010

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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.
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Metadata
Title
Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD
Authors
Simona E Budulac
Dirkje S Postma
Pieter S Hiemstra
Lisette IZ Kunz
Mateusz Siedlinski
Henriette A Smit
Judith M Vonk
Bea Rutgers
Wim Timens
H Marike Boezen
the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study group
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-11-60

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