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




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Fibrogenesis and Tissue Repair

, 4:24

Pulmonary Disease

Abstract

BackgroundCaveolin 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.

MethodsTwenty lung transplant recipients with BOS BOS, ninety without BOS BOS 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 patients and 10 BOS patients. Furthermore, single-time point Cav-1 serum levels were measured in 33 unmatched BOS patients and 60 healthy controls.

ResultsHomozygosity 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 patients than in the matched BOS 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 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.

ConclusionIn 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.

Keywordscaveolin 1 genetic polymorphism serum lung transplantation bronchiolitis obliterans syndrome Abbreviationsbpbase pair

BSAbovine serum albumin

ELISAenzyme-linked immunosorbent assay

SNPsingle-nucleotide polymorphism.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-1536-4-24 contains supplementary material, which is available to authorized users.

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Autor: Elisabeth A Kastelijn - Coline HM van Moorsel - Karin M Kazemier - Suzan M Roothaan - Henk JT Ruven - Johanna M Kwakke

Fuente: https://link.springer.com/







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