A genetic polymorphism in the CAV1 gene associates with the development of bronchiolitis obliterans syndrome after lung transplantation

Fibrogenesis & Tissue Repair

Jan C Grutters³  Diana A van Kessel¹  Pieter Zanen³  Ed A van de Graaf³  Johanna M Kwakkel-van Erp³  Henk JT Ruven²  Suzan M Roothaan⁴  Karin M Kazemier³  Coline HM van Moorsel³  Elisabeth A Kastelijn¹ 

[1] Centre of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Postbox 2500, NL-3420 EM, Nieuwegein, The Netherlands;Department of Clinical Chemistry, St Antonius Hospital, Postbox 2500, NL-3420 EM, Nieuwegein, The Netherlands;Division Heart and Lungs, University Medical Centre Utrecht, Postbox 85500, NL-3508 GA, Utrecht, The Netherlands;Department of Pathology, University Medical Centre Utrecht, Postbox 85500, NL-3508 GA, Utrecht, The Netherlands

关键词: bronchiolitis obliterans syndrome;    lung transplantation;    serum;    genetic polymorphism;    caveolin 1;   

Others  :  804065
DOI  :  10.1186/1755-1536-4-24

 received in 2011-07-12, accepted in 2011-11-01,  发布年份 2011

【 摘 要 】

Background

Caveolin 1 (Cav-1) is the primary structural component of cell membrane invaginations called 'caveolae'. Expression of Cav-1 is implicated in the pathogenesis of pulmonary fibrosis. Genetic polymorphisms in the CAV1 gene influence the function of Cav-1 in malignancies and associate with renal allograft fibrosis. Chronic allograft rejection after lung transplantation, called 'bronchiolitis obliterans syndrome' (BOS), is also characterised by the development of fibrosis.

In this study, we investigated whether CAV1 genotypes associate with BOS and whether Cav-1 serum levels are influenced by the CAV1 genotype and can be used as a biomarker to predict the development of BOS.

Methods

Twenty lung transplant recipients with BOS (BOS^pos), ninety without BOS (BOS^neg) and four hundred twenty-two healthy individuals donated DNA samples. Four SNPs in CAV1 were genotyped. Serial Cav-1 serum levels were measured in a matched cohort of 10 BOS^pos patients and 10 BOS^neg patients. Furthermore, single-time point Cav-1 serum levels were measured in 33 unmatched BOS^neg patients and 60 healthy controls.

Results

Homozygosity of the minor allele of rs3807989 was associated with an increased risk for BOS (odds ratio: 6.13; P = 0.0013). The median Cav-1 serum level was significantly higher in the BOS^pos patients than in the matched BOS^neg patients (P = 0.026). Longitudinal analysis did not show changes in Cav-1 serum levels over time in both groups. The median Cav-1 serum level in the group of 43 BOS^neg patients was lower than that in the healthy control group (P = 0.046).

In lung transplant recipients, homozygosity of the minor allele of rs3807989 and rs3807994 was associated with increased Cav-1 serum levels.

Conclusion

In lung transplant recipients, the CAV1 SNP rs3807989 was associated with the development of BOS and Cav-1 serum levels were influenced by the CAV1 genotype.

【 授权许可】

   
2011 Kastelijn et al; licensee BioMed Central Ltd.

【 图 表 】

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