Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.
Identifieur interne : 000082 ( PubMed/Corpus ); précédent : 000081; suivant : 000083Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.
Auteurs : S B Krintel ; C. Dehlendorff ; M L Hetland ; K. H Rslev-Petersen ; K K Andersen ; P. Junker ; J. P Denphant ; T. Ellingsen ; P. Ahlquist ; H M Lindegaard ; A. Linauskas ; A. Schlemmer ; M Y Dam ; I. Hansen ; H C Horn ; A. J Rgensen ; J. Raun ; C G Ammitzb Ll ; M. Stergaard ; K. Stengaard-Pedersen ; J S JohansenSource :
- The pharmacogenomics journal ; 2016.
Abstract
At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.
DOI: 10.1038/tpj.2015.30
PubMed: 25939484
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Dehlendorff</name><affiliation><nlm:affiliation>Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Hetland, M L" sort="Hetland, M L" uniqKey="Hetland M" first="M L" last="Hetland">M L Hetland</name><affiliation><nlm:affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="H Rslev Petersen, K" sort="H Rslev Petersen, K" uniqKey="H Rslev Petersen K" first="K" last="H Rslev-Petersen">K. H Rslev-Petersen</name><affiliation><nlm:affiliation>King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Andersen, K K" sort="Andersen, K K" uniqKey="Andersen K" first="K K" last="Andersen">K K Andersen</name><affiliation><nlm:affiliation>Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Junker, P" sort="Junker, P" uniqKey="Junker P" first="P" last="Junker">P. Junker</name><affiliation><nlm:affiliation>Department of Rheumatology, Odense University Hospital, Odense, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="P Denphant, J" sort="P Denphant, J" uniqKey="P Denphant J" first="J" last="P Denphant">J. 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Schlemmer</name><affiliation><nlm:affiliation>Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Dam, M Y" sort="Dam, M Y" uniqKey="Dam M" first="M Y" last="Dam">M Y Dam</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Hansen, I" sort="Hansen, I" uniqKey="Hansen I" first="I" last="Hansen">I. Hansen</name><affiliation><nlm:affiliation>Department of Rheumatology, Viborg Hospital, Viborg, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Horn, H C" sort="Horn, H C" uniqKey="Horn H" first="H C" last="Horn">H C Horn</name><affiliation><nlm:affiliation>Department of Rheumatology, Vejle Hospital, Vejle, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="J Rgensen, A" sort="J Rgensen, A" uniqKey="J Rgensen A" first="A" last="J Rgensen">A. J Rgensen</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Raun, J" sort="Raun, J" uniqKey="Raun J" first="J" last="Raun">J. Raun</name><affiliation><nlm:affiliation>King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Ammitzb Ll, C G" sort="Ammitzb Ll, C G" uniqKey="Ammitzb Ll C" first="C G" last="Ammitzb Ll">C G Ammitzb Ll</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey=" Stergaard, M" sort=" Stergaard, M" uniqKey=" Stergaard M" first="M" last=" Stergaard">M. Stergaard</name><affiliation><nlm:affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Stengaard Pedersen, K" sort="Stengaard Pedersen, K" uniqKey="Stengaard Pedersen K" first="K" last="Stengaard-Pedersen">K. Stengaard-Pedersen</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Johansen, J S" sort="Johansen, J S" uniqKey="Johansen J" first="J S" last="Johansen">J S Johansen</name><affiliation><nlm:affiliation>Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="doi">10.1038/tpj.2015.30</idno><idno type="RBID">pubmed:25939484</idno><idno type="pmid">25939484</idno><idno type="wicri:Area/PubMed/Corpus">000082</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.</title><author><name sortKey="Krintel, S B" sort="Krintel, S B" uniqKey="Krintel S" first="S B" last="Krintel">S B Krintel</name><affiliation><nlm:affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Dehlendorff, C" sort="Dehlendorff, C" uniqKey="Dehlendorff C" first="C" last="Dehlendorff">C. Dehlendorff</name><affiliation><nlm:affiliation>Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Hetland, M L" sort="Hetland, M L" uniqKey="Hetland M" first="M L" last="Hetland">M L Hetland</name><affiliation><nlm:affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="H Rslev Petersen, K" sort="H Rslev Petersen, K" uniqKey="H Rslev Petersen K" first="K" last="H Rslev-Petersen">K. H Rslev-Petersen</name><affiliation><nlm:affiliation>King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Andersen, K K" sort="Andersen, K K" uniqKey="Andersen K" first="K K" last="Andersen">K K Andersen</name><affiliation><nlm:affiliation>Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Junker, P" sort="Junker, P" uniqKey="Junker P" first="P" last="Junker">P. Junker</name><affiliation><nlm:affiliation>Department of Rheumatology, Odense University Hospital, Odense, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="P Denphant, J" sort="P Denphant, J" uniqKey="P Denphant J" first="J" last="P Denphant">J. P Denphant</name><affiliation><nlm:affiliation>Department of Rheumatology, Copenhagen University Hospital at Gentofte, Copenhagen, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Ellingsen, T" sort="Ellingsen, T" uniqKey="Ellingsen T" first="T" last="Ellingsen">T. Ellingsen</name><affiliation><nlm:affiliation>Diagnostic Centre, Regional Hospital Silkeborg, Silkeborg, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Ahlquist, P" sort="Ahlquist, P" uniqKey="Ahlquist P" first="P" last="Ahlquist">P. Ahlquist</name><affiliation><nlm:affiliation>Department of Rheumatology, Vejle Hospital, Vejle, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Lindegaard, H M" sort="Lindegaard, H M" uniqKey="Lindegaard H" first="H M" last="Lindegaard">H M Lindegaard</name><affiliation><nlm:affiliation>Department of Rheumatology, Odense University Hospital, Odense, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Linauskas, A" sort="Linauskas, A" uniqKey="Linauskas A" first="A" last="Linauskas">A. Linauskas</name><affiliation><nlm:affiliation>Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Schlemmer, A" sort="Schlemmer, A" uniqKey="Schlemmer A" first="A" last="Schlemmer">A. Schlemmer</name><affiliation><nlm:affiliation>Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Dam, M Y" sort="Dam, M Y" uniqKey="Dam M" first="M Y" last="Dam">M Y Dam</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Hansen, I" sort="Hansen, I" uniqKey="Hansen I" first="I" last="Hansen">I. Hansen</name><affiliation><nlm:affiliation>Department of Rheumatology, Viborg Hospital, Viborg, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Horn, H C" sort="Horn, H C" uniqKey="Horn H" first="H C" last="Horn">H C Horn</name><affiliation><nlm:affiliation>Department of Rheumatology, Vejle Hospital, Vejle, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="J Rgensen, A" sort="J Rgensen, A" uniqKey="J Rgensen A" first="A" last="J Rgensen">A. J Rgensen</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Raun, J" sort="Raun, J" uniqKey="Raun J" first="J" last="Raun">J. Raun</name><affiliation><nlm:affiliation>King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Ammitzb Ll, C G" sort="Ammitzb Ll, C G" uniqKey="Ammitzb Ll C" first="C G" last="Ammitzb Ll">C G Ammitzb Ll</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey=" Stergaard, M" sort=" Stergaard, M" uniqKey=" Stergaard M" first="M" last=" Stergaard">M. Stergaard</name><affiliation><nlm:affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Stengaard Pedersen, K" sort="Stengaard Pedersen, K" uniqKey="Stengaard Pedersen K" first="K" last="Stengaard-Pedersen">K. Stengaard-Pedersen</name><affiliation><nlm:affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Johansen, J S" sort="Johansen, J S" uniqKey="Johansen J" first="J S" last="Johansen">J S Johansen</name><affiliation><nlm:affiliation>Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The pharmacogenomics journal</title><idno type="e-ISSN">1473-1150</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="In-Data-Review"><PMID Version="1">25939484</PMID><DateCreated><Year>2016</Year><Month>03</Month><Day>22</Day></DateCreated><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1473-1150</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>2</Issue><PubDate><Year>2016</Year><Month>Apr</Month></PubDate></JournalIssue><Title>The pharmacogenomics journal</Title><ISOAbbreviation>Pharmacogenomics J.</ISOAbbreviation></Journal><ArticleTitle>Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.</ArticleTitle><Pagination><MedlinePgn>141-6</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/tpj.2015.30</ELocationID><Abstract><AbstractText>At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Krintel</LastName><ForeName>S B</ForeName><Initials>SB</Initials><AffiliationInfo><Affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dehlendorff</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hetland</LastName><ForeName>M L</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hørslev-Petersen</LastName><ForeName>K</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Andersen</LastName><ForeName>K K</ForeName><Initials>KK</Initials><AffiliationInfo><Affiliation>Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Junker</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Odense University Hospital, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pødenphant</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Copenhagen University Hospital at Gentofte, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ellingsen</LastName><ForeName>T</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Diagnostic Centre, Regional Hospital Silkeborg, Silkeborg, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ahlquist</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Vejle Hospital, Vejle, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lindegaard</LastName><ForeName>H M</ForeName><Initials>HM</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Odense University Hospital, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Linauskas</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schlemmer</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dam</LastName><ForeName>M Y</ForeName><Initials>MY</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hansen</LastName><ForeName>I</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Viborg Hospital, Viborg, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Horn</LastName><ForeName>H C</ForeName><Initials>HC</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Vejle Hospital, Vejle, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jørgensen</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raun</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Graasten, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ammitzbøll</LastName><ForeName>C G</ForeName><Initials>CG</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Østergaard</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stengaard-Pedersen</LastName><ForeName>K</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansen</LastName><ForeName>J S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Department of Medicine, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Oncology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>05</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Pharmacogenomics 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