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An interleukin 6-based genetic risk score strengthened with interleukin 10 polymorphisms associated with long-term kidney allograft outcomes.
Eskandari, Siawosh K; Gaya da Costa, Mariana; Faria, Bernardo; Petr, Vojtech; Azzi, Jamil R; Berger, Stefan P; Seelen, Marc A J; Damman, Jeffrey; Poppelaars, Felix.
Afiliación
  • Eskandari SK; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Gaya da Costa M; Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Faria B; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Petr V; Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Azzi JR; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Berger SP; Nephrology R&D Group, Institute for Research and Innovation in Health (i3S), São João University Hospital Center, University of Porto, Porto, Portugal.
  • Seelen MAJ; Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
  • Damman J; Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Poppelaars F; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Am J Transplant ; 22 Suppl 4: 45-57, 2022 12.
Article en En | MEDLINE | ID: mdl-36453708
Of all kidney transplants, half are still lost in the first decade after transplantation. Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss. In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p = .043 and p = .042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p < .001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10- polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Interleucina-10 Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Interleucina-10 Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos