Deceased-donor apolipoprotein L1 renal-risk variants have minimal effects on liver transplant outcomes

Casey R. Dorr, Barry I. Freedman, Pamela J. Hicks, W. Mark Brown, Gregory B. Russell, Bruce A. Julian, Stephen O. Pastan, Michael D. Gautreaux, Amutha Muthusamy, Srinath Chinnakotla, Vera Hauptfeld, Robert A. Bray, Allan D. Kirk, Jasmin Divers, Ajay K. Israni

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Abstract

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, endstage 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.

Original languageEnglish (US)
Article numbere0152775
JournalPloS one
Volume11
Issue number4
DOIs
StatePublished - Apr 2016

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Dorr, C. R., Freedman, B. I., Hicks, P. J., Brown, W. M., Russell, G. B., Julian, B. A., Pastan, S. O., Gautreaux, M. D., Muthusamy, A., Chinnakotla, S., Hauptfeld, V., Bray, R. A., Kirk, A. D., Divers, J., & Israni, A. K. (2016). Deceased-donor apolipoprotein L1 renal-risk variants have minimal effects on liver transplant outcomes. PloS one, 11(4), [e0152775]. https://doi.org/10.1371/journal.pone.0152775