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Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation

Genes & Immunity volume 10, pages 254–259 (2009)Cite this article

Abstract

Lung transplantation (LT) has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful LT is rejection of the transplanted organ where chemokines are pivotal mediators. Here, we test the relationship between copy number variation (CNV) in the CCL4L chemokine gene and rejection risk in LT patients (n=161). Patients with no acute rejection showed a significantly lower mean number of CCL4L copies than patients that showed acute rejection (1.66 vs 1.96, P=0.014), with an even greater number of gene copies seen in patients with more than one episode of acute rejection (1.66 vs 2.30, P=0.001). Additionally, patients with ⩾2 CCL4L copies had a significantly higher risk of acute rejection compared with patients that had 0–1 CCL4L copies (odds ratio 2.65; 95% confidence interval, 1.33–5.28; P=0.0046). A combined analysis of CCL4L CNV and the rs4796195 CCL4L single nucleotide polymorphism demonstrated that the effect of CCL4L copy number in acute rejection is mainly because of the number of copies of the CCL4L1 allelic variant. This finding constitutes the first report of CNV as a correlate factor in allograft rejection.

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Acknowledgements

We thank Justi Gil and Pepi Caro for their support in the genotyping process and Maria del Pilar Armengol for general support in the laboratory.

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Authors and Affiliations

  1. Laboratori d'Immunobiologia per a la Recerca i Aplicacions Diagnòstiques, Banc de Sang i Teixits, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain

    R Colobran, N Casamitjana, R Faner, E Pedrosa, R Pujol-Borrell, M Juan & E Palou

  2. Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain

    R Colobran, E Pedrosa, R Pujol-Borrell & M Juan

  3. Laboratori de Seguretat Transfusional, Banc de Sang i Teixits, Barcelona, Spain

    N Casamitjana

  4. Servei de Pneumologia, CIBERES, Hospital Universitari Vall d'Hebron, Barcelona, Spain

    A Roman

  5. Servei d'Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain

    J I Arostegui & M Juan

Authors
  1. R Colobran
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  2. N Casamitjana
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  3. A Roman
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  4. R Faner
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  5. E Pedrosa
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  6. J I Arostegui
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  7. R Pujol-Borrell
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  8. M Juan
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  9. E Palou
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Corresponding author

Correspondence to M Juan.

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Disclosure/conflict of interest

This study was supported by a grant from the Fundación para la Investigación y la Prevención del Sida en España (project number 36487/05), by the Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III (PI02/0278, PI07/0329), by the Red de Investigación en Enfermedades Renales (REDINREN) and by the PROFIT (FIT 010000-2006-38) of the Banc de Sang i Teixits R Faner and E Pedrosa are recipients of fellowships from Generalitat de Catalunya (2006 BP-B2 00022 and FIE 2006-00015 respectively).

The authors declare no conflict of interest or financial interests.

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Colobran, R., Casamitjana, N., Roman, A. et al. Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation. Genes Immun 10, 254–259 (2009). https://doi.org/10.1038/gene.2008.96

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  • DOI: https://doi.org/10.1038/gene.2008.96

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