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WFRF:(Granger Christopher B.)
 

Search: WFRF:(Granger Christopher B.) > (2020-2024) > Genetic determinant...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004660naa a2200505 4500
001oai:DiVA.org:uu-486690
003SwePub
008221017s2022 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4866902 URI
0247 a https://doi.org/10.3389/fgene.2022.9829552 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Attelind, Sofiau Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)sofat808
2451 0a Genetic determinants of apixaban plasma levels and their relationship to bleeding and thromboembolic events
264 c 2022-09-14
264 1b Frontiers Media S.A.c 2022
338 a electronic2 rdacarrier
520 a Apixaban is a direct oral anticoagulant, a factor Xa inhibitor, used for the prevention of ischemic stroke in patients with atrial fibrillation. Despite using recommended dosing a few patients might still experience bleeding or lack of efficacy that might be related to inappropriate drug exposure. We conducted a genome-wide association study using data from 1,325 participants in the pivotal phase three trial of apixaban with the aim to identify genetic factors affecting the pharmacokinetics of apixaban. A candidate gene analysis was also performed for pre-specified variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SULT1A1, with a subsequent analysis of all available polymorphisms within the candidate genes. Significant findings were further evaluated to assess a potential association with clinical outcome such as bleeding or thromboembolic events. No variant was consistently associated with an altered apixaban exposure on a genome-wide level. The candidate gene analyses showed a statistically significant association with a well-known variant in the drug transporter gene ABCG2 (c.421G > T, rs2231142). Patients carrying this variant had a higher exposure to apixaban [area under the curve (AUC), beta = 151 (95% CI 59-243), p = 0.001]. On average, heterozygotes displayed a 5% increase of AUC and homozygotes a 17% increase of AUC, compared with homozygotes for the wild-type allele. Bleeding or thromboembolic events were not significantly associated with ABCG2 rs2231142. This large genome-wide study demonstrates that genetic variation in the drug transporter gene ABCG2 is associated with the pharmacokinetics of apixaban. However, the influence of this finding on drug exposure was small, and further studies are needed to better understand whether it is of relevance for ischemic and bleeding events.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653 a factor Xa inhibitors
653 a apixaban
653 a atrial fibrillation
653 a genome-wide association study
653 a pharmacokinetics
653 a pharmacogenetics
653 a drug-related side effects and adverse reactions
7001 a Hallberg, Pär,d 1974-u Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)pahal677
7001 a Wadelius, Miau Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)miawadel
7001 a Hamberg, Anna-Karin,d 1964-u Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)anham086
7001 a Siegbahn, Agneta,d 1947-u Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Koagulation och inflammationsvetenskap4 aut0 (Swepub:uu)agsie424
7001 a Granger, Christopher B.u Duke Med, Duke Clin Res Inst, Durham, NC USA.4 aut
7001 a Lopes, Renato D.u Duke Med, Duke Clin Res Inst, Durham, NC USA.4 aut
7001 a Alexander, John H.u Duke Med, Duke Clin Res Inst, Durham, NC USA.4 aut
7001 a Wallentin, Lars,d 1943-u Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)larswall
7001 a Eriksson, Niclas,d 1978-u Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)nieri103
7102 a Uppsala universitetb Klinisk farmakogenomik och osteoporos4 org
7730 t Frontiers in Geneticsd : Frontiers Media S.A.g 13q 13x 1664-8021
8564 u https://doi.org/10.3389/fgene.2022.982955y Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:1704035/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-486690
8564 8u https://doi.org/10.3389/fgene.2022.982955

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