{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:22:06Z","timestamp":1772166126811,"version":"3.50.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"national science foundation,china","award":["81960579"],"award-info":[{"award-number":["81960579"]}]},{"DOI":"10.13039\/501100010012","name":"national aerospace science foundation of china","doi-asserted-by":"publisher","award":["81660559"],"award-info":[{"award-number":["81660559"]}],"id":[{"id":"10.13039\/501100010012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In recent years, the incidence rate of vivax malaria recurrence still had 3.1% in Yunnan Province population after eradication therapy using primaquine (PQ). In order to understand the specific failure reasons for preventing vivax malaria relapses, a preliminary exploration on the CYP2D6 enzyme activity was carried out in the vivax malaria patients in Yunnan Province population by analysing mutational polymorphism in the coding region of CYP2D6 gene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood samples were collected from vivax malaria patients with suspected relapse (SR) and non-relapsed (NR) malaria in Yunnan Province. The DNA fragments containing 9 exons regions of human CYP2D6 gene were amplified by performing PCR and sequenced. The sequencing results were aligned by using DNAStar 11.0 to obtain the coding DNA sequence (CDS) of CYP2D6 gene. DnaSP 6.11.01 software was used to identify mutant polymorphisms and haplotypes of the CDS chain. The waterfall function of GenVisR package in R\u00a0was utilized to visualize the mutational landscape. The alleles of CYP2D6 gene were identified according to the criteria prescribed by Human Cytochrome P450 (CYP) Allele Nomenclature Committee Database and the CYP2D6 enzyme activity was predicted based on diploid genotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 320 maternal CDS chains, including 63 from SR group and 257 from NR group, were obtained. Twelve mutant loci, including c.31 (rs769259), c.100 (rs1065852), c.271 (rs28371703), c.281 (rs28371704), c.294 (rs28371705), c.297 (rs200269944), c.336 (rs1081003), c.408 (rs1058164), c.505 (rs5030865), c.801 (rs28371718), c.886 (rs16947), and c.1,457 (rs1135840) were observed on the 640 CDS chains (including 320 maternal and 320 paternal chains). The high-frequency mutation at rs1135840 (0.703) and low-frequency mutation, such as rs28371703, were detected only in the SR group. The frequency of mutant rs1058164 and rs1135840 were significantly increased in the SR group (\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$${x}^{2}$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:msup>\n                              <mml:mrow>\n                                <mml:mi>x<\/mml:mi>\n                              <\/mml:mrow>\n                              <mml:mn>2<\/mml:mn>\n                            <\/mml:msup>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      = 4.468, 5.889,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05), as opposed to the NR group. Of the 23 haplotypes (from Hap_1 to Hap_23), the nomenclatures of 11 allelic forms could be found: Hap_3 was non-mutant, Hap_2 accounted for the highest frequency (36.9%, 236\/640), and Hap_9 had the most complex sequence structure, containing 7 loci mutations. Allele *10 was the most frequent among these genotypes (0.423). Among the allele *10 standard named genotypes, *1\/*10, *1\/*1 and *2\/*10 were significantly more frequent in the NR group (\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$${x}^{2}$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:msup>\n                              <mml:mrow>\n                                <mml:mi>x<\/mml:mi>\n                              <\/mml:mrow>\n                              <mml:mn>2<\/mml:mn>\n                            <\/mml:msup>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      = 3.911,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05) and all showed uncompromised enzyme activity; the impaired genotype *10\/*39 was more frequent in the SR group (\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$${x}^{2}$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:msup>\n                              <mml:mrow>\n                                <mml:mi>x<\/mml:mi>\n                              <\/mml:mrow>\n                              <mml:mn>2<\/mml:mn>\n                            <\/mml:msup>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      = 10.050,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05), and genotype *4\/*4was detected only in the SR group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the patients receiving PQ dosage in Yunnan Province population, both rs1135840 single nucleotide polymorphism and *10 allele form was common in the CYP2D6 gene. Low-frequency mutation sites, such as rs28371703, were only presented in patients with vivax malaria relapse.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-021-03988-5","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T13:32:03Z","timestamp":1638279123000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prediction of the CYP2D6 enzymatic activity based on investigating of the CYP2D6 genotypes around the vivax malaria patients in Yunnan Province, China"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-8675","authenticated-orcid":false,"given":"Ying","family":"Dong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengni","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Canglin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"3988_CR1","unstructured":"WHO. Guidelines for the treatment of malaria. 3rd Edn. Geneva: World Health Organization. 2015, 257\u201361."},{"key":"3988_CR2","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1056\/NEJMc1301936","volume":"369","author":"JW Bennett","year":"2013","unstructured":"Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, et al. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med. 2013;369:1381\u20132.","journal-title":"N Engl J Med"},{"key":"3988_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2016.03.011","volume":"161","author":"SR Marcsisin","year":"2016","unstructured":"Marcsisin SR, Reichard G, Pybus BS. Primaquine pharmacology in the context of CYP 2D6 pharmacogenomics: current state of the art. Pharmacol Ther. 2016;161:1\u201310.","journal-title":"Pharmacol Ther"},{"key":"3988_CR4","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.ejmech.2008.08.011","volume":"44","author":"N Vale","year":"2009","unstructured":"Vale N, Moreira R, Gomes P. Primaquine revisited six decades after its discovery. Eur J Med Chem. 2009;44:937\u201353.","journal-title":"Eur J Med Chem"},{"key":"3988_CR5","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/1475-2875-11-259","volume":"11","author":"BS Pybus","year":"2012","unstructured":"Pybus BS, Sousa JC, Jin X, Ferguson JA, Christian RE, Barnhart R, et al. CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine. Malar J. 2012;11:259.","journal-title":"Malar J"},{"key":"3988_CR6","doi-asserted-by":"publisher","first-page":"15007","DOI":"10.1038\/npjgenmed.2015.7","volume":"1","author":"GP Twist","year":"2016","unstructured":"Twist GP, Gaedigk A, Miller NA, Farrow EG, Willig LK, Dinwiddie DL, et al. Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, CYP2D6, from whole-genome sequences. NPJ Genom Med. 2016;1:15007.","journal-title":"NPJ Genom Med"},{"key":"3988_CR7","doi-asserted-by":"crossref","unstructured":"Baird JK, Louisa M, Noviyanti R, Ekawati L, Elyazar I, Subekti D, et al. Association of impaired cytochrome P450 2D6 activity genotype and phenotype with therapeutic efficacy of primaquine treatment for latent Plasmodium vivax malaria. JAMA Netw Open. 2018;1:e181449.","DOI":"10.1001\/jamanetworkopen.2018.1449"},{"key":"3988_CR8","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1186\/s12879-019-4357-9","volume":"19","author":"X He","year":"2019","unstructured":"He X, Pan M, Zeng W, Zou C, Pi L, Qin Y, et al. Multiple relapses of Plasmodium vivax malaria acquired from West Africa and association with poor metabolizer CYP2D6 variant: a case report. BMC Infect Dis. 2019;19:704.","journal-title":"BMC Infect Dis"},{"key":"3988_CR9","doi-asserted-by":"crossref","unstructured":"Friedrich DC, Genro JP, Sortica VA, Suarez-Kurtz G, de Moraes ME, Pena SD, et al. Distribution of CYP2D6 alleles and phenotypes in the Brazilian population. PLoS One. 2014;9:e110691.","DOI":"10.1371\/journal.pone.0110691"},{"key":"3988_CR10","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1186\/1475-2875-13-488","volume":"13","author":"RJ Ingram","year":"2014","unstructured":"Ingram RJ, Crenna-Darusallam C, Soebianto S, Noviyanti R, Baird JK. The clinical and public health problem of relapse despite primaquine therapy: case review of repeated relapses of Plasmodium vivax acquired in Papua New Guinea. Malar J. 2014;13:488.","journal-title":"Malar J"},{"key":"3988_CR11","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/sj.clpt.6100406","volume":"83","author":"A Gaedigk","year":"2008","unstructured":"Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther. 2008;83:234\u201342.","journal-title":"Clin Pharmacol Ther"},{"key":"3988_CR12","doi-asserted-by":"crossref","unstructured":"Silvino ACR, Costa GL, Ara\u00fajo FCF, Ascher DB, Pires DEV, Fontes CJF, et al. Variation in human cytochrome P-450 drug-metabolism genes: a gateway to the understanding of Plasmodium vivax relapses. PLoS One. 2016;11: e0160172.","DOI":"10.1371\/journal.pone.0160172"},{"key":"3988_CR13","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/1475-2875-12-213","volume":"12","author":"WHO Malaria Policy Advisory Committee and Secretariat","year":"2013","unstructured":"WHO Malaria Policy Advisory Committee and Secretariat. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of March 2013 meeting. Malar J. 2013;12:213.","journal-title":"Malar J"},{"key":"3988_CR14","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s12936-017-1787-y","volume":"16","author":"BE Barber","year":"2017","unstructured":"Barber BE, Rajahram GS, Grigg MJ, William T, Anstey NM. World Malaria Report: time to acknowledge Plasmodium knowlesi malaria. Malar J. 2017;16:135.","journal-title":"Malar J"},{"key":"3988_CR15","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/1475-2875-12-212","volume":"12","author":"BS Pybus","year":"2013","unstructured":"Pybus BS, Marcsisin SR, Jin X, Deye G, Sousa JC, Li Q, et al. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J. 2013;12:212.","journal-title":"Malar J"},{"key":"3988_CR16","first-page":"399","volume":"37","author":"Y Dong","year":"2019","unstructured":"Dong Y, Liu SP, Xu YC, Liu Y, Deng Y, Chen MN. Mutations and predicted structure change of G6PD isolated from a patient with primaquine-induced hemolysis in Yunnan Province. Chin J Parasitol Parasit Dis. 2019;37:399\u2013405 (in Chinese).","journal-title":"Chin J Parasitol Parasit Dis"},{"key":"3988_CR17","first-page":"146","volume":"38","author":"SP Liu","year":"2020","unstructured":"Liu SP, Dong Y, Xu YC, Liu Y, Deng Y, Zhang CL, et al. The mutation polymorphism of G6PD gene coding region in vivax malaria patients in Yunnan Province, China. Chin J Parasitol Parasit Dis. 2020;38:146\u201351 (in Chinese).","journal-title":"Chin J Parasitol Parasit Dis"},{"key":"3988_CR18","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12936-021-03685-3","volume":"20","author":"H Huang","year":"2021","unstructured":"Huang H, Dong Y, Xu Y, Deng Y, Zhang C, Liu S, et al. The association of CYP2D6 gene polymorphisms in the full-length coding region with higher recurrence rate of vivax malaria in Yunnan Province, China. Malar J. 2021;20:160.","journal-title":"Malar J"},{"key":"3988_CR19","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12936-015-0556-z","volume":"14","author":"JH Yin","year":"2015","unstructured":"Yin JH, Yan H, Huang F, Li M, Xiao HH, Zhou SS, et al. Establishing a China malaria diagnosis reference laboratory network for malaria elimination. Malar J. 2015;14:40.","journal-title":"Malar J"},{"key":"3988_CR20","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1186\/s12936-020-03477-1","volume":"19","author":"Y Dong","year":"2020","unstructured":"Dong Y, Deng Y, Xu Y, Chen M, Wei C, Zhang C, et al. Analysis of initial laboratory diagnosis of malaria and its accuracy compared with re-testing from 2013 to 2018 in Yunnan Province, China. Malar J. 2020;19:409.","journal-title":"Malar J"},{"key":"3988_CR21","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1186\/s12936-019-2950-4","volume":"18","author":"A Daher","year":"2019","unstructured":"Daher A, Aljayyoussi G, Pereira D, Lacerda MVG, Alexandre MAA, Nascimento CT, et al. Pharmacokinetics\/pharmacodynamics of chloroquine and artemisinin-based combination therapy with primaquine. Malar J. 2019;18:325.","journal-title":"Malar J"},{"key":"3988_CR22","doi-asserted-by":"crossref","unstructured":"Sistonen J, Fuselli S, LevoA, Sajantila A. CYP2D6 genotyping by a multiplex primer extension reaction. Clin Chem. 2005;51:1291\u20135.","DOI":"10.1373\/clinchem.2004.046466"},{"key":"3988_CR23","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.gene.2019.04.012","volume":"703","author":"AA Swadi","year":"2019","unstructured":"Swadi AA, Mohammad BI, Hadi NR, Al-Aubaidy HA. Correlation of CYP2D6 allelic polymorphism to outcome of acute coronary syndrome in mid-Euphrates Iraqi patients on metoprolol therapy. Gene. 2019;703:112\u20139.","journal-title":"Gene"},{"key":"3988_CR24","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12936-017-2139-7","volume":"17","author":"LW Brasil","year":"2018","unstructured":"Brasil LW, Rodrigues-Soares F, Santoro AB, Almeida ACG, K\u00fchn A, Ramasawmy R, et al. CYP2D6 activity and the risk of recurrence of Plasmodium vivax malaria in the Brazilian Amazon: a prospective cohort study. Malar J. 2018;17:57.","journal-title":"Malar J"},{"key":"3988_CR25","unstructured":"NM_000106.6 Database. https:\/\/www.pharmvar.org\/gene\/CYP2D6. Accessed 09 Nov 2020."},{"key":"3988_CR26","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1002\/cpt.1643","volume":"107","author":"C Nofziger","year":"2020","unstructured":"Nofziger C, Turner AJ, Sangkuhl K, Whirl-Carrillo M, Ag\u00fandez JAG, Black JL, et al. PharmVar GeneFocus: CYP2D6. Clin Pharmacol Ther. 2020;107:154\u201370.","journal-title":"Clin Pharmacol Ther"},{"key":"3988_CR27","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s40801-019-00177-4","volume":"7","author":"G Kamenski","year":"2020","unstructured":"Kamenski G, Ayazseven S, Berndt A, Fink W, Kamenski L, Zehetmayer S, et al. Clinical relevance of CYP2D6 polymorphisms in patients of an Austrian Medical Practice: a family practice-based observational study. Drugs Real World Outcomes. 2020;7:63\u201373.","journal-title":"Drugs Real World Outcomes"},{"key":"3988_CR28","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/gim.2016.80","volume":"19","author":"A Gaedigk","year":"2017","unstructured":"Gaedigk A, Sangkuhl K, Whirl-Carrillo M, Klein T, Leeder JS. Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med. 2017;19:69\u201376.","journal-title":"Genet Med"},{"key":"3988_CR29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/jpm8020015","volume":"8","author":"A Gaedigk","year":"2018","unstructured":"Gaedigk A, Dinh JC, Jeong H, Prasad B, Leeder JS. Ten years\u2019 experience with the CYP2D6 activity score: a perspective on future investigations to improve clinical predictions for precision therapeutics. J Pers Med. 2018;8:15.","journal-title":"J Pers Med"},{"key":"3988_CR30","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/cts.12692","volume":"13","author":"KE Caudle","year":"2020","unstructured":"Caudle KE, Sangkuhl K, Whirl-Carrillo M, Swen JJ, Haidar CE, Klein TE, et al. Standardizing CYP2D6 genotype to phenotype translation: consensus recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group. Clin Transl Sci. 2020;13:116\u201324.","journal-title":"Clin Transl Sci"},{"key":"3988_CR31","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1097\/00008571-200103000-00005","volume":"11","author":"T Shimada","year":"2001","unstructured":"Shimada T, Tsumura F, Yamazaki H, Guengerich FP, Inoue K. Characterization of (+\/-)-bufuralol hydroxylation activities in liver microsomes of Japanese and Caucasian subjects genotyped for CYP2D6. Pharmacogenetics. 2001;11:143\u201356.","journal-title":"Pharmacogenetics"},{"key":"3988_CR32","unstructured":"https:\/\/www.ncbi.nlm.nih.gov\/genome\/gdv\/browser\/?context=gene&acc=128989."},{"key":"3988_CR33","doi-asserted-by":"crossref","unstructured":"Salles PF, Perce-da-Silva DS, Rossi AD, Raposo LR, Ramirez Ramirez AD, Pereira Bastos OM, et al. CYP2D6 allele frequency in five malaria vivax endemic areas from Brazilian Amazon region. Front Pharmacol. 2021;12:542342.","DOI":"10.3389\/fphar.2021.542342"},{"key":"3988_CR34","doi-asserted-by":"publisher","first-page":"e02056","DOI":"10.1128\/AAC.02056-19","volume":"64","author":"ACR Silvino","year":"2020","unstructured":"Silvino ACR, Kano FS, Costa MA, Fontes CJF, Soares IS, de Brito CFA, et al. Novel insights into Plasmodium vivax therapeutic failure: CYP2D6 activity and time of exposure to malaria modulate the risk of recurrence. Antimicrob Agents Chemother. 2020;64:e02056-e2119.","journal-title":"Antimicrob Agents Chemother"},{"key":"3988_CR35","doi-asserted-by":"crossref","unstructured":"Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, et al. Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012;91:321\u20136.","DOI":"10.1038\/clpt.2011.287"},{"key":"3988_CR36","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/hmg\/ddt417","volume":"23","author":"D Wang","year":"2014","unstructured":"Wang D, Poi MJ, Sun X, Gaedigk A, Leeder JS, Sadee W. Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity. Hum Mol Genet. 2014;23:268\u201378.","journal-title":"Hum Mol Genet"},{"key":"3988_CR37","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1007\/s00210-019-01651-0","volume":"392","author":"AN Dong","year":"2019","unstructured":"Dong AN, Ahemad N, Pan Y, Palanisamy UD, Yiap BC, Ong CE. Functional and structural characterisation of common cytochrome P450 2D6 allelic variants-roles of Pro34 and Thr107 in catalysis and inhibition. Naunyn Schmiedebergs Arch Pharmacol. 2019;392:1015\u201329.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"3988_CR38","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12936-018-2190-z","volume":"17","author":"JK Baird","year":"2018","unstructured":"Baird JK, Battle KE, Howes RE. Primaquine ineligibility in anti-relapse therapy of Plasmodium vivax malaria: the problem of G6PD deficiency and cytochrome P-450 2D6 polymorphisms. Malar J. 2018;17:42.","journal-title":"Malar J"},{"key":"3988_CR39","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1097\/01.fpc.0000239974.69464.f2","volume":"17","author":"J Sistonen","year":"2007","unstructured":"Sistonen J, Sajantila A, Lao O, Corander J, Barbujani G, Fuselli S. CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet Genomics. 2007;17:93\u2013101.","journal-title":"Pharmacogenet Genomics"},{"key":"3988_CR40","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1182\/blood-2014-12-614123","volume":"125","author":"A Mayor","year":"2015","unstructured":"Mayor A, Alano P. Bone marrow reticulocytes: a Plasmodium vivax affair? Blood. 2015;125:1203\u20135.","journal-title":"Blood"},{"key":"3988_CR41","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1182\/blood-2010-04-202911","volume":"117","author":"PA Buffet","year":"2011","unstructured":"Buffet PA, Safeukui I, Deplaine G, Brousse V, Prendki V, Thellier M, et al. The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. Blood. 2011;117:381\u201392.","journal-title":"Blood"},{"key":"3988_CR42","doi-asserted-by":"publisher","first-page":"471","DOI":"10.4269\/ajtmh.2001.65.471","volume":"65","author":"EC Duarte","year":"2001","unstructured":"Duarte EC, Pang LW, Ribeiro LC, Fontes CJ. Association of subtherapeutic dosages of a standard drug regimen with failures in preventing relapses of vivax malaria. Am J Trop Med Hyg. 2001;65:471\u20136.","journal-title":"Am J Trop Med Hyg"},{"key":"3988_CR43","doi-asserted-by":"publisher","first-page":"e15891","DOI":"10.1097\/MD.0000000000015891","volume":"98","author":"HH Nguyen","year":"2019","unstructured":"Nguyen HH, Ma TTH, Vu NP, Bach QTN, Vu TH, Nguyen TD, et al. Single nucleotide and structural variants of CYP2D6 gene in Kinh Vietnamese population. Medicine (Baltimore). 2019;98:e15891.","journal-title":"Medicine (Baltimore)"},{"key":"3988_CR44","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s12936-016-1145-5","volume":"15","author":"PL St Jean","year":"2016","unstructured":"St Jean PL, Xue Z, Carter N, Koh GC, Duparc S, Taylor M, et al. Tafenoquine treatment of Plasmodium vivax malaria: suggestive evidence that CYP2D6 reduced metabolism is not associated with relapse in the Phase 2b DETECTIVE trial. Malar J. 2016;15:97.","journal-title":"Malar J"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-021-03988-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-021-03988-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-021-03988-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T13:36:36Z","timestamp":1638279396000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-021-03988-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,25]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3988"],"URL":"https:\/\/doi.org\/10.1186\/s12936-021-03988-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-714877\/v1","asserted-by":"object"}]},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,25]]},"assertion":[{"value":"14 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The design and protocol of the study was approved by the Yunnan Institute of Parasitic Diseases and Ethical Committee (Ethical Approval No.: 2019 Yunnan Ethics Auditing No. 5). The purpose of the study was explained to the subjects or their relatives, genetic testing was performed on stored blood samples obtained as part of the routine diagnostic work-up of patients with fever who were suspected to have malaria.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors provided their consent for the publication of this report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicted interest regarding the publication of the present manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"448"}}