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Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes

BACKGROUND: Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance). C...

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Autores principales: Dorr, Casey R., Freedman, Barry I., Hicks, Pamela J., Brown, W. Mark, Russell, Gregory B., Julian, Bruce A., Pastan, Stephen O., Gautreaux, Michael D., Muthusamy, Amutha, Chinnakotla, Srinath, Hauptfeld, Vera, Bray, Robert A., Kirk, Allan D., Divers, Jasmin, Israni, Ajay K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824450/
https://www.ncbi.nlm.nih.gov/pubmed/27054572
http://dx.doi.org/10.1371/journal.pone.0152775
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author Dorr, Casey R.
Freedman, Barry I.
Hicks, Pamela J.
Brown, W. Mark
Russell, Gregory B.
Julian, Bruce A.
Pastan, Stephen O.
Gautreaux, Michael D.
Muthusamy, Amutha
Chinnakotla, Srinath
Hauptfeld, Vera
Bray, Robert A.
Kirk, Allan D.
Divers, Jasmin
Israni, Ajay K.
author_facet Dorr, Casey R.
Freedman, Barry I.
Hicks, Pamela J.
Brown, W. Mark
Russell, Gregory B.
Julian, Bruce A.
Pastan, Stephen O.
Gautreaux, Michael D.
Muthusamy, Amutha
Chinnakotla, Srinath
Hauptfeld, Vera
Bray, Robert A.
Kirk, Allan D.
Divers, Jasmin
Israni, Ajay K.
author_sort Dorr, Casey R.
collection PubMed
description BACKGROUND: Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance). Circulating APOL1 protein is synthesized primarily in the liver and hydrodynamic gene delivery of APOL1 G1 and G2 risk variants has caused hepatic necrosis in a murine model. METHODS: To evaluate the impact of these variants in liver transplantation, this multicenter study investigated the association of APOL1 G1 and G2 alleles in deceased African American liver donors with allograft survival. Transplant recipients were followed for liver allograft survival using data from the Scientific Registry of Transplant Recipients. RESULTS: Of the 639 liver donors evaluated, 247 had no APOL1 risk allele, 300 had 1 risk allele, and 92 had 2 risk alleles. Graft failure assessed at 15 days, 6 months, 1 year and total was not significantly associated with donor APOL1 genotype (p-values = 0.25, 0.19, 0.67 and 0.89, respectively). CONCLUSIONS: In contrast to kidney transplantation, deceased-donor APOL1 G1 and G2 risk variants do not significantly impact outcomes in liver transplantation.
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spelling pubmed-48244502016-04-22 Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes Dorr, Casey R. Freedman, Barry I. Hicks, Pamela J. Brown, W. Mark Russell, Gregory B. Julian, Bruce A. Pastan, Stephen O. Gautreaux, Michael D. Muthusamy, Amutha Chinnakotla, Srinath Hauptfeld, Vera Bray, Robert A. Kirk, Allan D. Divers, Jasmin Israni, Ajay K. PLoS One Research Article BACKGROUND: Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance). Circulating APOL1 protein is synthesized primarily in the liver and hydrodynamic gene delivery of APOL1 G1 and G2 risk variants has caused hepatic necrosis in a murine model. METHODS: To evaluate the impact of these variants in liver transplantation, this multicenter study investigated the association of APOL1 G1 and G2 alleles in deceased African American liver donors with allograft survival. Transplant recipients were followed for liver allograft survival using data from the Scientific Registry of Transplant Recipients. RESULTS: Of the 639 liver donors evaluated, 247 had no APOL1 risk allele, 300 had 1 risk allele, and 92 had 2 risk alleles. Graft failure assessed at 15 days, 6 months, 1 year and total was not significantly associated with donor APOL1 genotype (p-values = 0.25, 0.19, 0.67 and 0.89, respectively). CONCLUSIONS: In contrast to kidney transplantation, deceased-donor APOL1 G1 and G2 risk variants do not significantly impact outcomes in liver transplantation. Public Library of Science 2016-04-07 /pmc/articles/PMC4824450/ /pubmed/27054572 http://dx.doi.org/10.1371/journal.pone.0152775 Text en © 2016 Dorr et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dorr, Casey R.
Freedman, Barry I.
Hicks, Pamela J.
Brown, W. Mark
Russell, Gregory B.
Julian, Bruce A.
Pastan, Stephen O.
Gautreaux, Michael D.
Muthusamy, Amutha
Chinnakotla, Srinath
Hauptfeld, Vera
Bray, Robert A.
Kirk, Allan D.
Divers, Jasmin
Israni, Ajay K.
Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes
title Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes
title_full Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes
title_fullStr Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes
title_full_unstemmed Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes
title_short Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes
title_sort deceased-donor apolipoprotein l1 renal-risk variants have minimal effects on liver transplant outcomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824450/
https://www.ncbi.nlm.nih.gov/pubmed/27054572
http://dx.doi.org/10.1371/journal.pone.0152775
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