Caveolin-1 rs4730751 single-nucleotide polymorphism may not influence kidney transplant allograft survival

Mehdi Maanaoui,Romain Larrue,Nicolas Pottier,Rémi Lenain,Marie Frimat,Cynthia Van Der Hauwaert,Benjamin Lopez,Marc Hazzan,François Glowacki,François Provôt,Aghilès Hamroun,Franck Broly,Jean-Baptiste Gibier,Christelle Cauffiez,Benjamin Hennart,Grégoire Savary

doi:10.1038/s41598-019-52079-8

Mehdi Maanaoui, Romain Larrue + Show 14 more

Open Access

https://doi.org/10.1038/s41598-019-52079-8

Copy DOI

Abstract

Caveolin-1 is a protein (encoded by the CAV1 gene) supposedly harboring a protective effect against fibrosis. CAV1 rs4730751 single nucleotide polymorphism (SNP) AA genotype was initially associated with lower graft survival compared to non-AA. However, subsequent studies could not find the same effect. CAV1 rs4730751 SNP was investigated on 918 kidney donors. Multivariate Cox-model analyses were performed to evaluate risk factors for graft loss. Longitudinal changes on long-term estimated glomerular filtration rate (eGFRs) were evaluated with a linear mixed model. Histopathological findings from protocolled biopsies after 3 months post transplantation were also analyzed. Donor CAV1 rs4730751 genotyping proportions were 7.1% for AA, 41.6% for AC and 51.3% for CC. The AA genotype, compared to non-AA, was not associated with lower graft survival censored or not for death (multivariate analysis: HR = 1.23 [0.74–2.05] and HR = 1.27 [0.84–1.92]). Linear mixed model on long-term eGFRs revealed also no significant difference according to the genotype, yet we observed a trend. AA genotype was also not associated with a higher degree of fibrosis index on protocolled kidney biopsies at 3 months. To conclude, donor CAV1 rs4730751 SNP may impact on kidney transplantation outcomes, but this study could not confirm this hypothesis.

Highlights

This seminal study has led to the evaluation of CAV1 Single Nucleotide Polymorphism (SNP) involvement in various diseases, such as chronic kidney diseases[17], pancreas transplantation[18], Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) vasculitis[19] or cancers[20,21]
Considering these uncertainties, we carried out a study in a large-scaled cohort in order to evaluate the impact of donor CAV1 rs4730751 SNP on kidney transplantation outcomes, using a combined analysis of graft survivals, long-term estimated Glomerular Filtration rates and histopathological data from systematic kidney biopsies
2016, 918 donors for kidney transplantation were genotyped for the CAV1 rs4730751 SNP

Summary

Introduction

This seminal study has led to the evaluation of CAV1 SNPs involvement in various diseases, such as chronic kidney diseases[17], pancreas transplantation[18], Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) vasculitis[19] or cancers[20,21]. The enthusiasm has been somewhat tempered by the controversies that have risen about the real impact of CAV1 SNPs in the field of kidney transplantation. Graft survival was not associated with CAV1 rs4730751 SNP either from donors or recipients in two other cohorts[23,24] Considering these uncertainties, we carried out a study in a large-scaled cohort in order to evaluate the impact of donor CAV1 rs4730751 SNP on kidney transplantation outcomes, using a combined analysis of graft survivals, long-term estimated Glomerular Filtration rates (eGFRs) and histopathological data from systematic kidney biopsies

Objectives

Methods

Results

Conclusion