The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

Major complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and...

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Main Authors: Katharina Rump, Tim Rahmel, Anna-Maria Rustige, Matthias Unterberg, Hartmuth Nowak, Björn Koos, Peter Schenker, Richard Viebahn, Michael Adamzik, Lars Bergmann
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/9/6/1421
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author Katharina Rump
Tim Rahmel
Anna-Maria Rustige
Matthias Unterberg
Hartmuth Nowak
Björn Koos
Peter Schenker
Richard Viebahn
Michael Adamzik
Lars Bergmann
author_facet Katharina Rump
Tim Rahmel
Anna-Maria Rustige
Matthias Unterberg
Hartmuth Nowak
Björn Koos
Peter Schenker
Richard Viebahn
Michael Adamzik
Lars Bergmann
author_sort Katharina Rump
collection DOAJ
description Major complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and we explored the effect of AQP3 polymorphism on immune cell function and its association with graft rejection and CMV infection in 237 adult patients within 12 months after transplantation. AQP3 promoter polymorphism was molecular and functional characterized. Kaplan–Meier plots evaluated the relationship between genotypes and the incidence of CMV infection and graft rejection. AQP3 A(−1431)G A-allele was associated with enhanced immune cell migration and AQP3 expression in T-cells. The incidences of rejection were 45.4% for the A-allele and 27.1% for G-allele carriers (<i>p</i> = 0.005) and the A-allele was a strong risk factor (hazard ratio (HR): 1.95; 95% CI: 1.216 to 3.127; <i>p</i> = 0.006). The incidences for CMV infection were 21% for A-allele and 35% for G-allele carriers (<i>p</i> = 0.013) and G-allele was an independent risk factor (<i>p</i> = 0.023), with a doubled risk for CMV infection (HR: 1.9; 95% CI: 1.154 to 3.128; <i>p</i> = 0.012). Hence, A-allele confers more resistance against CMV infection, but susceptibility to graft rejection mediated by T-cells. Thus, AQP3-genotype adapted management of immunosuppression and antiviral prophylaxis after kidney transplantation seems prudent.
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spelling doaj.art-6616c8d19995459cb32ccee039bae7702023-11-20T03:09:16ZengMDPI AGCells2073-44092020-06-0196142110.3390/cells9061421The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell MigrationKatharina Rump0Tim Rahmel1Anna-Maria Rustige2Matthias Unterberg3Hartmuth Nowak4Björn Koos5Peter Schenker6Richard Viebahn7Michael Adamzik8Lars Bergmann9Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyChirurgische Universitätsklinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyChirurgische Universitätsklinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44801 Bochum, GermanyMajor complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and we explored the effect of AQP3 polymorphism on immune cell function and its association with graft rejection and CMV infection in 237 adult patients within 12 months after transplantation. AQP3 promoter polymorphism was molecular and functional characterized. Kaplan–Meier plots evaluated the relationship between genotypes and the incidence of CMV infection and graft rejection. AQP3 A(−1431)G A-allele was associated with enhanced immune cell migration and AQP3 expression in T-cells. The incidences of rejection were 45.4% for the A-allele and 27.1% for G-allele carriers (<i>p</i> = 0.005) and the A-allele was a strong risk factor (hazard ratio (HR): 1.95; 95% CI: 1.216 to 3.127; <i>p</i> = 0.006). The incidences for CMV infection were 21% for A-allele and 35% for G-allele carriers (<i>p</i> = 0.013) and G-allele was an independent risk factor (<i>p</i> = 0.023), with a doubled risk for CMV infection (HR: 1.9; 95% CI: 1.154 to 3.128; <i>p</i> = 0.012). Hence, A-allele confers more resistance against CMV infection, but susceptibility to graft rejection mediated by T-cells. Thus, AQP3-genotype adapted management of immunosuppression and antiviral prophylaxis after kidney transplantation seems prudent.https://www.mdpi.com/2073-4409/9/6/1421AQP3aquaporin 3polymorphismkidney transplantationAQP3 −1431 A/Grs3860987
spellingShingle Katharina Rump
Tim Rahmel
Anna-Maria Rustige
Matthias Unterberg
Hartmuth Nowak
Björn Koos
Peter Schenker
Richard Viebahn
Michael Adamzik
Lars Bergmann
The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration
Cells
AQP3
aquaporin 3
polymorphism
kidney transplantation
AQP3 −1431 A/G
rs3860987
title The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration
title_full The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration
title_fullStr The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration
title_full_unstemmed The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration
title_short The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration
title_sort aquaporin 3 promoter polymorphism 1431 a g is associated with acute graft rejection and cytomegalovirus infection in kidney recipients due to altered immune cell migration
topic AQP3
aquaporin 3
polymorphism
kidney transplantation
AQP3 −1431 A/G
rs3860987
url https://www.mdpi.com/2073-4409/9/6/1421
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