Evidence map›Paper›PMID 30442921›Full record

Observational studyThe pharmacogenomics journal2019

Identification of genetic variants associated with tacrolimus metabolism in kidney transplant recipients by extreme phenotype sampling and next generation sequencing.

Casey R Dorr, Baolin Wu, Rory P Remmel, Amutha Muthusamy, David P Schladt, Juan E Abrahante, Weihua Guan, Roslyn B Mannon, Arthur J Matas, William S Oetting and 3 more

Open access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The pharmacogenomics journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Trial
  2. Hidden in Plain Sight: Low Tacrolimus Metabolism Doubles Kidney Transplant Failure and Drives Infection Related Mortality.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Tacrolimus troughs and genetic determinants of metabolism in kidney transplant recipients: A comparison of four ancestry groups.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019
    Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Casey R DorrHennepin Healthcare Research Institute, Minneapolis, MN, USA. cdorr@hhrinstitute.org.
Baolin WuDepartment of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
Rory P RemmelDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
Amutha MuthusamyHennepin Healthcare Research Institute, Minneapolis, MN, USA.
David P SchladtHennepin Healthcare Research Institute, Minneapolis, MN, USA.
Juan E AbrahanteInformatics Institute, University of Minnesota, Minneapolis, MN, USA.
Weihua GuanDepartment of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
Roslyn B MannonDepartments of Medicine and Surgery, University of Alabama, Birmingham, AL, USA.
Arthur J MatasDepartment of Surgery, University of Minnesota, Minneapolis, MN, USA.
William S OettingExperimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Pamala A JacobsonExperimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Ajay K IsraniHennepin Healthcare Research Institute, Minneapolis, MN, USA.
for DeKAF Genomics
University of Minnesota · USHennepin Healthcare Research Institute · US

Funding

Pharmacogenomics of Immune Suppressants in Kidney TransplantationU19AI070119 · NIAID · UNIVERSITY OF MINNESOTA · PI MATAS, ARTHUR J · 2006 to 2016
$17.1M
Long-term Deterioration of Kidney Allograft FunctionU01AI058013 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MATAS, ARTHUR J · 2005 to 2010
$10.2M
Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant RecipientsK01AI130409 · NIAID · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI DORR, CASEY R · 2018 to 2022
$724k
Molecular and Cellular Analysis of Allograft Loss in Kidney Transplant BiopsiesR21AI171826 · NIAID · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI DORR, CASEY R · 2022 to 2023
$406k
NIAID NIH HHS 5U01AI058013NIAID NIH HHS 5U19AI070119NIAID NIH HHS K01 AI130409NIAID NIH HHS K01AI130409NIAID NIH HHS R21 AI171826NIAID NIH HHS U01 AI058013NIAID NIH HHS U19 AI070119
6 · The paper itself

Abstract

An extreme phenotype sampling (EPS) model with targeted next-generation sequencing (NGS) identified genetic variants associated with tacrolimus (Tac) metabolism in subjects from the Deterioration of Kidney Allograft Function (DeKAF) Genomics cohort which included 1,442 European Americans (EA) and 345 African Americans (AA). This study included 48 subjects separated into 4 groups of 12 (AA high, AA low, EA high, EA low). Groups were selected by the extreme phenotype of dose-normalized Tac trough concentrations after adjusting for common genetic variants and clinical factors. NGS spanned > 3 Mb of 28 genes and identified 18,661 genetic variants (3961 previously unknown). A group of 125 deleterious variants, by SIFT analysis, were associated with Tac troughs in EAs (burden test, p = 0.008), CYB5R2 was associated with Tac troughs in AAs (SKAT, p = 0.00079). In CYB5R2, rs61733057 (increased allele frequency in AAs) was predicted to disrupt protein function by SIFT and PolyPhen2 analysis. The variants merit further validation.

Indexed as

AdolescentAdultAgedAged, 80 and overBlack or African AmericanCytochromes b5FemaleGene FrequencyGenetic VariationGenotypeGraft RejectionHigh-Throughput Nucleotide SequencingHumansImmunosuppressive AgentsKidney TransplantationMaleCytochromes b5Immunosuppressive AgentsTacrolimus

Identifiers

PMID30442921
PMCPMC6522337
OpenAlexW2900771606

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.