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Multicenter Study
. 2010 May 20;11(1):60.
doi: 10.1186/1465-9921-11-60.

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

Simona E Budulac  1 , Dirkje S Postma, Pieter S Hiemstra, Lisette I Z Kunz, Mateusz Siedlinski, Henriette A Smit, Judith M Vonk, Bea Rutgers, Wim Timens, H Marike Boezen; Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study group
Collaborators, Affiliations
Multicenter Study

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

Simona E Budulac et al. Respir Res. .

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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Figures

Figure 1
Figure 1
Estimated effects of MRP1 genotypes on level of FEV1 in COPD patients. FEV1 = forced expiratory volume in one second. N= Number of individuals. Squares represent the regression coefficient (B) and vertical bars represent 95% confidence interval (CI). Wild type was set to zero as the reference category. The analyses are adjusted for age, gender, height and packyears.
Figure 2
Figure 2
Estimated effects of MRP1 genotypes on inflammatory cells in bronchial biopsies of COPD patients. 2a: Number of plasma cells according to rs212093 genotype. 2b: Number of neutrophils according to rs212093 genotype. 2c: Number of mast cells according to rs212093 genotype. 2d: Number of macrophages according to for rs212093 genotype.
Figure 3
Figure 3
Estimated effects of MRP1 genotypes on inflammatory cells in bronchial biopsies of COPD patients. Number of macrophages according to rs4781699 genotype. N = number of individuals. Data are presented as natural logarithm of each type of cells in bronchial biopsies. Different numbers for the SNP genotypes are due to missing data on genotype or inflammatory cells. Squares represent the regression coefficient (B) and vertical bars the 95% confidence interval (CI). Wild type was set to zero as the reference category. The analyses are adjusted for age, gender and packyears.
Figure 4
Figure 4
MRP1 SNPs and MRP1 protein levels of COPD patients and controls. 4a: MRP1 protein levels according to rs4148382 genotype in COPD patients. 4b: MRP1 protein levels according to rs4148382 genotype in controls. 4c: MRP1 protein levels according to rs4781699 genotype in COPD patients. 4d: MRP1 protein levels according to rs4781699 genotype in controls. N= number of individuals.
Figure 5
Figure 5
Summary of MRP1 SNPs' associations for COPD patients. FEV1 = forced expiratory volume in one second; MRP1 = multidrug resistance-associated protein-1; ↑ = positive association; ↓ = negative association; - = no association.
See this image and copyright information in PMC

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