Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population
Identifieur interne : 000199 ( Main/Exploration ); précédent : 000198; suivant : 000200Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population
Auteurs : William Kudzi [Ghana] ; Samuel Yao Ahorhorlu [Ghana] ; Bartholomew Dzudzor [Ghana] ; Edeghonghon Olayemi [Ghana] ; Edmund Tetteh Nartey [Ghana] ; Richard Harry Asmah [Ghana]Source :
- BMC Research Notes [ 1756-0500 ] ; 2016.
Abstract
Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within
One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34–58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10–72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin.
This study provides data on
Url:
DOI: 10.1186/s13104-016-2306-x
PubMed: 27938396
PubMed Central: 5148898
Affiliations:
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GP 4236, Accra, Ghana</nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra</wicri:regionArea><placeName><settlement type="city">Accra</settlement><region nuts="2">Région du Grand Accra</region></placeName><orgName type="university">Université du Ghana</orgName></affiliation></author><author><name sortKey="Ahorhorlu, Samuel Yao" sort="Ahorhorlu, Samuel Yao" uniqKey="Ahorhorlu S" first="Samuel Yao" last="Ahorhorlu">Samuel Yao Ahorhorlu</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra, Ghana</nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra</wicri:regionArea><placeName><settlement type="city">Accra</settlement><region nuts="2">Région du Grand Accra</region></placeName><orgName type="university">Université du Ghana</orgName></affiliation></author><author><name sortKey="Dzudzor, Bartholomew" sort="Dzudzor, Bartholomew" uniqKey="Dzudzor B" first="Bartholomew" last="Dzudzor">Bartholomew Dzudzor</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Department of Medical Biochemistry, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. GP 143, Accra, Ghana</nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medical Biochemistry, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. GP 143, Accra</wicri:regionArea><placeName><settlement type="city">Accra</settlement><region nuts="2">Région du Grand Accra</region></placeName><orgName type="university">Université du Ghana</orgName></affiliation></author><author><name sortKey="Olayemi, Edeghonghon" sort="Olayemi, Edeghonghon" uniqKey="Olayemi E" first="Edeghonghon" last="Olayemi">Edeghonghon Olayemi</name><affiliation wicri:level="4"><nlm:aff id="Aff3">Department of Haematology, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra, Ghana</nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Haematology, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra</wicri:regionArea><placeName><settlement type="city">Accra</settlement><region nuts="2">Région du Grand Accra</region></placeName><orgName type="university">Université du Ghana</orgName></affiliation></author><author><name sortKey="Nartey, Edmund Tetteh" sort="Nartey, Edmund Tetteh" uniqKey="Nartey E" first="Edmund Tetteh" last="Nartey">Edmund Tetteh Nartey</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra, Ghana</nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra</wicri:regionArea><placeName><settlement type="city">Accra</settlement><region nuts="2">Région du Grand Accra</region></placeName><orgName type="university">Université du Ghana</orgName></affiliation></author><author><name sortKey="Asmah, Richard Harry" sort="Asmah, Richard Harry" uniqKey="Asmah R" first="Richard Harry" last="Asmah">Richard Harry Asmah</name><affiliation wicri:level="4"><nlm:aff id="Aff4">Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. GP 143, Accra, Ghana</nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. GP 143, Accra</wicri:regionArea><placeName><settlement type="city">Accra</settlement><region nuts="2">Région du Grand Accra</region></placeName><orgName type="university">Université du Ghana</orgName></affiliation></author></analytic><series><title level="j">BMC Research Notes</title><idno type="eISSN">1756-0500</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within <italic>VKORC1</italic>, <italic>CYP2C9</italic> and <italic>CYP4F2</italic> were determined in patients on either high or low warfarin maintenance dose.</p></sec><sec><title>Results</title><p>One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34–58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10–72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin. <italic>CYP2C9*</italic>2 and <italic>CYP2C9*</italic>3 variant alleles were not detected. <italic>VKORC1</italic> variant allele was observed at 6% and <italic>CYP4F2</italic> variant allele was observed at 41%. Duration of patients on warfarin therapy was marginally associated with high warfarin dose (adjusted OR = 1.01 [95% CI 1.00–1.02], p = 0.033) while the odds of heterozygous individuals (G/A) for VKORC1 gene to have high warfarin dose compared to persons with homozygous (G/G) (adjusted OR = 0.06 [95% CI 0.01–0.63], p = 0.019). Age, gender, diagnosis, presence of side effects and other medications were not associated with warfarin dose (p = 0.05).</p></sec><sec><title>Conclusion</title><p>This study provides data on <italic>VKORC1</italic> and <italic>CYP4F2</italic> variants among an indigenous African population. Duration of patients on warfarin therapy was marginally associated with high warfarin dose. <italic>CYP2C9</italic>*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Daly, Ak" uniqKey="Daly A">AK Daly</name></author><author><name sortKey="King, Bp" uniqKey="King B">BP King</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Walraven, C" uniqKey="Van Walraven C">C van Walraven</name></author><author><name sortKey="Hart, Rg" uniqKey="Hart R">RG Hart</name></author><author><name sortKey="Connolly, S" uniqKey="Connolly S">S Connolly</name></author><author><name sortKey="Austin, Pc" uniqKey="Austin P">PC Austin</name></author><author><name sortKey="Mant, J" uniqKey="Mant J">J Mant</name></author><author><name sortKey="Hobbs, Fd" uniqKey="Hobbs F">FD 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uniqKey="Geisslinger G">G Geisslinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aomori, T" uniqKey="Aomori T">T Aomori</name></author><author><name sortKey="Yamamoto, K" uniqKey="Yamamoto K">K Yamamoto</name></author><author><name sortKey="Oguchi Katayama, A" uniqKey="Oguchi Katayama A">A Oguchi-Katayama</name></author><author><name sortKey="Kawai, Y" uniqKey="Kawai Y">Y Kawai</name></author><author><name sortKey="Ishidao, T" uniqKey="Ishidao T">T Ishidao</name></author><author><name sortKey="Mitani, Y" uniqKey="Mitani Y">Y Mitani</name></author><author><name sortKey="Kogo, Y" uniqKey="Kogo Y">Y Kogo</name></author><author><name sortKey="Lezhava, A" uniqKey="Lezhava A">A Lezhava</name></author><author><name sortKey="Fujita, Y" uniqKey="Fujita Y">Y Fujita</name></author><author><name sortKey="Obayashi, K" uniqKey="Obayashi K">K Obayashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kudzi, W" uniqKey="Kudzi 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uniqKey="Suarez Kurtz G">G Suarez-Kurtz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scott, Sa" uniqKey="Scott S">SA Scott</name></author><author><name sortKey="Jaremko, M" uniqKey="Jaremko M">M Jaremko</name></author><author><name sortKey="Lubitz, Sa" uniqKey="Lubitz S">SA Lubitz</name></author><author><name sortKey="Kornreich, R" uniqKey="Kornreich R">R Kornreich</name></author><author><name sortKey="Halperin, Jl" uniqKey="Halperin J">JL Halperin</name></author><author><name sortKey="Desnick, Rj" uniqKey="Desnick R">RJ Desnick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scott, Sa" uniqKey="Scott S">SA Scott</name></author><author><name sortKey="Edelmann, L" uniqKey="Edelmann L">L Edelmann</name></author><author><name sortKey="Kornreich, R" uniqKey="Kornreich R">R Kornreich</name></author><author><name sortKey="Desnick, Rj" uniqKey="Desnick R">RJ Desnick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Sw" uniqKey="Huang S">SW Huang</name></author><author><name sortKey="Chen, Hs" uniqKey="Chen H">HS Chen</name></author><author><name sortKey="Wang, Xq" uniqKey="Wang X">XQ Wang</name></author><author><name sortKey="Huang, L" uniqKey="Huang L">L Huang</name></author><author><name sortKey="Xu, Dl" uniqKey="Xu D">DL Xu</name></author><author><name sortKey="Hu, Xj" uniqKey="Hu X">XJ Hu</name></author><author><name sortKey="Huang, Zh" uniqKey="Huang Z">ZH Huang</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Chen, Km" uniqKey="Chen K">KM Chen</name></author><author><name sortKey="Xiang, Dk" uniqKey="Xiang D">DK Xiang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Ghana</li></country><region><li>Région du Grand Accra</li></region><settlement><li>Accra</li></settlement><orgName><li>Université du Ghana</li></orgName></list><tree><country name="Ghana"><region name="Région du Grand Accra"><name sortKey="Kudzi, William" sort="Kudzi, William" uniqKey="Kudzi W" first="William" last="Kudzi">William Kudzi</name></region><name sortKey="Ahorhorlu, Samuel Yao" sort="Ahorhorlu, Samuel Yao" uniqKey="Ahorhorlu S" first="Samuel Yao" last="Ahorhorlu">Samuel Yao Ahorhorlu</name><name sortKey="Asmah, Richard Harry" sort="Asmah, Richard Harry" uniqKey="Asmah R" first="Richard Harry" last="Asmah">Richard Harry Asmah</name><name sortKey="Dzudzor, Bartholomew" sort="Dzudzor, Bartholomew" uniqKey="Dzudzor B" first="Bartholomew" last="Dzudzor">Bartholomew Dzudzor</name><name sortKey="Nartey, Edmund Tetteh" sort="Nartey, Edmund Tetteh" uniqKey="Nartey E" first="Edmund Tetteh" last="Nartey">Edmund Tetteh Nartey</name><name sortKey="Olayemi, Edeghonghon" sort="Olayemi, Edeghonghon" uniqKey="Olayemi E" first="Edeghonghon" last="Olayemi">Edeghonghon Olayemi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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