Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol.

ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics Aged Aged, 80 and over Allopurinol / pharmacology Cytokines / genetics Ethnicity Female Genome-Wide Association Study Glucose Transport Proteins, Facilitative / antagonists & inhibitors Humans Male Middle Aged Neoplasm Proteins / genetics Oxypurinol / pharmacology Prognosis Uric Acid / metabolism

Journal

Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741

Informations de publication

Date de publication:
09 2019
Historique:
received: 07 11 2018
accepted: 22 02 2019
pubmed: 30 3 2019
medline: 12 5 2020
entrez: 30 3 2019
Statut: ppublish

Résumé

Allopurinol, which lowers uric acid (UA) concentration, is increasingly being recognized for its benefits in cardiovascular and renal disease. However, response to allopurinol is variable. We gathered samples from 4,446 multiethnic subjects for a genome-wide association study of allopurinol response. Consistent with previous studies, we observed that the Q141K variant in ABCG2 (rs2231142), which encodes the efflux pump breast cancer resistance protein (BCRP), associated with worse response to allopurinol. However, for the first time this association reached genome-wide level significance (P = 8.06 × 10

Identifiants

DOI: 10.1002/cpt.1439 PMID: 30924126 PMC: PMC6941886
pubmed: 30924126
doi: 10.1002/cpt.1439
pmc: PMC6941886
mid: NIHMS1061487
doi:

Substances chimiques

ABCG2 protein, human 0
ATP Binding Cassette Transporter, Subfamily G, Member 2 0
Cytokines 0
GREM2 protein, human 0
Glucose Transport Proteins, Facilitative 0
Neoplasm Proteins 0
SLC2A9 protein, human 0
Uric Acid 268B43MJ25
Allopurinol 63CZ7GJN5I
Oxypurinol G97OZE5068

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

623-631

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK103729
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133786
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM061390
Pays : United States

Informations de copyright

© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.

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Auteurs

Deanna J Brackman (DJ)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.

Sook Wah Yee (SW)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.

Osatohanmwen J Enogieru (OJ)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.

Christian Shaffer (C)

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Dilrini Ranatunga (D)

Kaiser Permanente Northern California Division of Research, Oakland, California, USA.

Joshua C Denny (JC)

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Wei-Qi Wei (WQ)

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Yoichiro Kamatani (Y)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Michiaki Kubo (M)

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Dan M Roden (DM)

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Eric Jorgenson (E)

Kaiser Permanente Northern California Division of Research, Oakland, California, USA.

Kathleen M Giacomini (KM)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Institute of Human Genetics, University of California San Francisco, San Francisco, California, USA.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Transporteurs ABC › Sous-famille G des transporteurs à cassette liant l'ATP › Membre-2 de la sous-famille G des transporteurs à cassette liant l'ATP › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Allopurinol › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Caractéristiques de la population › Ethnies › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Transporteurs de glucose par diffusion facilitée › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Oxipurinol › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Diagnostic › Pronostic › Genome-Wide Association and Functional Studies...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Purinones › Xanthines › Acide urique › Genome-Wide Association and Functional Studies...