Sökning: onr:"swepub:oai:DiVA.org:uu-486690" > Genetic determinant...
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000 | 04660naa a2200505 4500 | |
001 | oai:DiVA.org:uu-486690 | |
003 | SwePub | |
008 | 221017s2022 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4866902 URI |
024 | 7 | a https://doi.org/10.3389/fgene.2022.9829552 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Attelind, Sofiau Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)sofat808 |
245 | 1 0 | a Genetic determinants of apixaban plasma levels and their relationship to bleeding and thromboembolic events |
264 | c 2022-09-14 | |
264 | 1 | b 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 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe |
650 | 7 | a 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 | |
700 | 1 | a Hallberg, Pär,d 1974-u Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)pahal677 |
700 | 1 | a Wadelius, Miau Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)miawadel |
700 | 1 | a Hamberg, Anna-Karin,d 1964-u Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)anham086 |
700 | 1 | a Siegbahn, Agneta,d 1947-u Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Koagulation och inflammationsvetenskap4 aut0 (Swepub:uu)agsie424 |
700 | 1 | a Granger, Christopher B.u Duke Med, Duke Clin Res Inst, Durham, NC USA.4 aut |
700 | 1 | a Lopes, Renato D.u Duke Med, Duke Clin Res Inst, Durham, NC USA.4 aut |
700 | 1 | a Alexander, John H.u Duke Med, Duke Clin Res Inst, Durham, NC USA.4 aut |
700 | 1 | a Wallentin, Lars,d 1943-u Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)larswall |
700 | 1 | a Eriksson, Niclas,d 1978-u Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)nieri103 |
710 | 2 | a Uppsala universitetb Klinisk farmakogenomik och osteoporos4 org |
773 | 0 | t Frontiers in Geneticsd : Frontiers Media S.A.g 13q 13x 1664-8021 |
856 | 4 | u https://doi.org/10.3389/fgene.2022.982955y Fulltext |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1704035/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-486690 |
856 | 4 8 | u https://doi.org/10.3389/fgene.2022.982955 |
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