Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s Disease
Further to the wellestablished association between apolipoprotein E (APOE) and Alzheimer’s disease, this gene has also been implicated in both susceptibility to, and dementia in, Parkinson’s disease (PD). However studies to date have produced contradictory findings. We conducted a case-control study...
Gespeichert in:
| Veröffentlicht in: | Journal of neurology 2009-03, Vol.256 (3), p.493-498 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 498 |
|---|---|
| container_issue | 3 |
| container_start_page | 493 |
| container_title | Journal of neurology |
| container_volume | 256 |
| creator | Williams-Gray, C. H. Goris, A. Saiki, M. Foltynie, T. Compston, D. A. S. Sawcer, S. J. Barker, R. A. |
| description | Further to the wellestablished association between apolipoprotein E (APOE) and Alzheimer’s disease, this gene has also been implicated in both susceptibility to, and dementia in, Parkinson’s disease (PD). However studies to date have produced contradictory findings. We conducted a case-control study in a population of 528 PD patients and 512 healthy controls and found no significant difference in allele or genotype distribution of APOE between the two groups. An updated meta-analysis showed a modest increase of APOE-ε2 carriers amongst PD patients compared to controls [
P
= 0.017, OR = 1.16 (95 % CI 1.03–1.31)]. 107 of our patients were incident cases participating in a populationbased epidemiological study. Longitudinal follow-up of this cohort over a mean of 5.0 ± 0.7 years from diagnosis revealed no significant impact of APOE-ε4 carrier status on risk of dementia or rate of cognitive decline. An updated meta-analysis indicated an over-representation of APOE-ε4 carriers amongst PD dementia compared to non dementia cases [OR 1.74 (1.36–2.23),
P
= 1 × 10
–4
], although small sample sizes, heterogeneity of odds ratios and publication bias may have confounded this finding. In conclusion, our study does not support previously reported associations between APOE genotype and susceptibility to, or cognitive decline in, PD. An updated meta-analysis indicates any association with PD susceptibility is at most modest, an observation with important implications for further study of this issue. Large scale longitudinal studies would be best placed to further evaluate any impact of APOE genotype on cognitive decline in PD. |
| doi_str_mv | 10.1007/s00415-009-0119-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67195030</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1697511531</sourcerecordid><originalsourceid>FETCH-LOGICAL-c496t-c0a8d6e23791903836130d46cb38dba27060ea87b4303fd1acfc2b1cfa1463823</originalsourceid><addsrcrecordid>eNqFkcFu1DAQhi1ERZfCA3BBFhLcUmbiOLGPVWkBqRIc4Gw5jlO5zdrBkxz2xmvwejxJvdoVlZAQB8uH-eafGX2MvUI4R4DuPQE0KCsAXQGirtQTtsFG1BU2Uj9lGxANVFLI5pQ9J7oDAFUKz9gpagFKQLdh48WcpjCnOafFh8iv-K2PadnNnlviludA93y0bkmZj-XRSs7PS-jDFJYdXxK3ceCD3_q4BMtLwleb70OkFH___EX8QyBvyb9gJ6OdyL88_mfs-_XVt8tP1c2Xj58vL24q1-h2qRxYNbS-Fp1GDUKJFgUMTet6oYbe1h204K3q-kaAGAe0bnR1j2602LRC1eKMvTvklnt-rJ4Wsw1l4Wmy0aeVTNuhllCa_wfWIJWWuE988xd4l9YcyxGmRoUSNcoC4QFyORFlP5o5h63NO4Ng9qrMQZUpqsxelVGl5_UxeO23fnjsOLopwNsjYMnZacw2ukB_uBqLWNnth9cHjkop3vr8uOG_pz8AkLurtg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>218151915</pqid></control><display><type>article</type><title>Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s Disease</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Williams-Gray, C. H. ; Goris, A. ; Saiki, M. ; Foltynie, T. ; Compston, D. A. S. ; Sawcer, S. J. ; Barker, R. A.</creator><creatorcontrib>Williams-Gray, C. H. ; Goris, A. ; Saiki, M. ; Foltynie, T. ; Compston, D. A. S. ; Sawcer, S. J. ; Barker, R. A.</creatorcontrib><description>Further to the wellestablished association between apolipoprotein E (APOE) and Alzheimer’s disease, this gene has also been implicated in both susceptibility to, and dementia in, Parkinson’s disease (PD). However studies to date have produced contradictory findings. We conducted a case-control study in a population of 528 PD patients and 512 healthy controls and found no significant difference in allele or genotype distribution of APOE between the two groups. An updated meta-analysis showed a modest increase of APOE-ε2 carriers amongst PD patients compared to controls [
P
= 0.017, OR = 1.16 (95 % CI 1.03–1.31)]. 107 of our patients were incident cases participating in a populationbased epidemiological study. Longitudinal follow-up of this cohort over a mean of 5.0 ± 0.7 years from diagnosis revealed no significant impact of APOE-ε4 carrier status on risk of dementia or rate of cognitive decline. An updated meta-analysis indicated an over-representation of APOE-ε4 carriers amongst PD dementia compared to non dementia cases [OR 1.74 (1.36–2.23),
P
= 1 × 10
–4
], although small sample sizes, heterogeneity of odds ratios and publication bias may have confounded this finding. In conclusion, our study does not support previously reported associations between APOE genotype and susceptibility to, or cognitive decline in, PD. An updated meta-analysis indicates any association with PD susceptibility is at most modest, an observation with important implications for further study of this issue. Large scale longitudinal studies would be best placed to further evaluate any impact of APOE genotype on cognitive decline in PD.</description><identifier>ISSN: 0340-5354</identifier><identifier>EISSN: 1432-1459</identifier><identifier>DOI: 10.1007/s00415-009-0119-8</identifier><identifier>PMID: 19308307</identifier><identifier>CODEN: JNRYA9</identifier><language>eng</language><publisher>Darmstadt: Steinkopff-Verlag</publisher><subject>Alzheimer's disease ; Apolipoprotein E2 - genetics ; Apolipoprotein E4 - genetics ; Apolipoproteins ; Apolipoproteins E - genetics ; Biological and medical sciences ; Case-Control Studies ; Cognition Disorders - complications ; Cognition Disorders - genetics ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Dementia ; Dementia - complications ; Dementia - genetics ; Family medical history ; Female ; Follow-Up Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype & phenotype ; Health risk assessment ; Humans ; Longitudinal studies ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Meta-analysis ; Middle Aged ; Neurology ; Neuropsychological Tests ; Neuroradiology ; Neurosciences ; Odds Ratio ; Original Communication ; Parkinson Disease - complications ; Parkinson Disease - genetics ; Parkinson's disease ; Risk Factors ; Sequence Analysis, DNA</subject><ispartof>Journal of neurology, 2009-03, Vol.256 (3), p.493-498</ispartof><rights>Steinkopff-Verlag 2009</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-c0a8d6e23791903836130d46cb38dba27060ea87b4303fd1acfc2b1cfa1463823</citedby><cites>FETCH-LOGICAL-c496t-c0a8d6e23791903836130d46cb38dba27060ea87b4303fd1acfc2b1cfa1463823</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00415-009-0119-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00415-009-0119-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21354575$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19308307$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Williams-Gray, C. H.</creatorcontrib><creatorcontrib>Goris, A.</creatorcontrib><creatorcontrib>Saiki, M.</creatorcontrib><creatorcontrib>Foltynie, T.</creatorcontrib><creatorcontrib>Compston, D. A. S.</creatorcontrib><creatorcontrib>Sawcer, S. J.</creatorcontrib><creatorcontrib>Barker, R. A.</creatorcontrib><title>Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s Disease</title><title>Journal of neurology</title><addtitle>J Neurol</addtitle><addtitle>J Neurol</addtitle><description>Further to the wellestablished association between apolipoprotein E (APOE) and Alzheimer’s disease, this gene has also been implicated in both susceptibility to, and dementia in, Parkinson’s disease (PD). However studies to date have produced contradictory findings. We conducted a case-control study in a population of 528 PD patients and 512 healthy controls and found no significant difference in allele or genotype distribution of APOE between the two groups. An updated meta-analysis showed a modest increase of APOE-ε2 carriers amongst PD patients compared to controls [
P
= 0.017, OR = 1.16 (95 % CI 1.03–1.31)]. 107 of our patients were incident cases participating in a populationbased epidemiological study. Longitudinal follow-up of this cohort over a mean of 5.0 ± 0.7 years from diagnosis revealed no significant impact of APOE-ε4 carrier status on risk of dementia or rate of cognitive decline. An updated meta-analysis indicated an over-representation of APOE-ε4 carriers amongst PD dementia compared to non dementia cases [OR 1.74 (1.36–2.23),
P
= 1 × 10
–4
], although small sample sizes, heterogeneity of odds ratios and publication bias may have confounded this finding. In conclusion, our study does not support previously reported associations between APOE genotype and susceptibility to, or cognitive decline in, PD. An updated meta-analysis indicates any association with PD susceptibility is at most modest, an observation with important implications for further study of this issue. Large scale longitudinal studies would be best placed to further evaluate any impact of APOE genotype on cognitive decline in PD.</description><subject>Alzheimer's disease</subject><subject>Apolipoprotein E2 - genetics</subject><subject>Apolipoprotein E4 - genetics</subject><subject>Apolipoproteins</subject><subject>Apolipoproteins E - genetics</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Cognition Disorders - complications</subject><subject>Cognition Disorders - genetics</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Dementia</subject><subject>Dementia - complications</subject><subject>Dementia - genetics</subject><subject>Family medical history</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype & phenotype</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Longitudinal studies</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Meta-analysis</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Neuropsychological Tests</subject><subject>Neuroradiology</subject><subject>Neurosciences</subject><subject>Odds Ratio</subject><subject>Original Communication</subject><subject>Parkinson Disease - complications</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Risk Factors</subject><subject>Sequence Analysis, DNA</subject><issn>0340-5354</issn><issn>1432-1459</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkcFu1DAQhi1ERZfCA3BBFhLcUmbiOLGPVWkBqRIc4Gw5jlO5zdrBkxz2xmvwejxJvdoVlZAQB8uH-eafGX2MvUI4R4DuPQE0KCsAXQGirtQTtsFG1BU2Uj9lGxANVFLI5pQ9J7oDAFUKz9gpagFKQLdh48WcpjCnOafFh8iv-K2PadnNnlviludA93y0bkmZj-XRSs7PS-jDFJYdXxK3ceCD3_q4BMtLwleb70OkFH___EX8QyBvyb9gJ6OdyL88_mfs-_XVt8tP1c2Xj58vL24q1-h2qRxYNbS-Fp1GDUKJFgUMTet6oYbe1h204K3q-kaAGAe0bnR1j2602LRC1eKMvTvklnt-rJ4Wsw1l4Wmy0aeVTNuhllCa_wfWIJWWuE988xd4l9YcyxGmRoUSNcoC4QFyORFlP5o5h63NO4Ng9qrMQZUpqsxelVGl5_UxeO23fnjsOLopwNsjYMnZacw2ukB_uBqLWNnth9cHjkop3vr8uOG_pz8AkLurtg</recordid><startdate>20090301</startdate><enddate>20090301</enddate><creator>Williams-Gray, C. H.</creator><creator>Goris, A.</creator><creator>Saiki, M.</creator><creator>Foltynie, T.</creator><creator>Compston, D. A. S.</creator><creator>Sawcer, S. J.</creator><creator>Barker, R. A.</creator><general>Steinkopff-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20090301</creationdate><title>Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s Disease</title><author>Williams-Gray, C. H. ; Goris, A. ; Saiki, M. ; Foltynie, T. ; Compston, D. A. S. ; Sawcer, S. J. ; Barker, R. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-c0a8d6e23791903836130d46cb38dba27060ea87b4303fd1acfc2b1cfa1463823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alzheimer's disease</topic><topic>Apolipoprotein E2 - genetics</topic><topic>Apolipoprotein E4 - genetics</topic><topic>Apolipoproteins</topic><topic>Apolipoproteins E - genetics</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Cognition Disorders - complications</topic><topic>Cognition Disorders - genetics</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Dementia</topic><topic>Dementia - complications</topic><topic>Dementia - genetics</topic><topic>Family medical history</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype & phenotype</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Longitudinal studies</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Meta-analysis</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Neuropsychological Tests</topic><topic>Neuroradiology</topic><topic>Neurosciences</topic><topic>Odds Ratio</topic><topic>Original Communication</topic><topic>Parkinson Disease - complications</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Risk Factors</topic><topic>Sequence Analysis, DNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Williams-Gray, C. H.</creatorcontrib><creatorcontrib>Goris, A.</creatorcontrib><creatorcontrib>Saiki, M.</creatorcontrib><creatorcontrib>Foltynie, T.</creatorcontrib><creatorcontrib>Compston, D. A. S.</creatorcontrib><creatorcontrib>Sawcer, S. J.</creatorcontrib><creatorcontrib>Barker, R. A.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Williams-Gray, C. H.</au><au>Goris, A.</au><au>Saiki, M.</au><au>Foltynie, T.</au><au>Compston, D. A. S.</au><au>Sawcer, S. J.</au><au>Barker, R. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s Disease</atitle><jtitle>Journal of neurology</jtitle><stitle>J Neurol</stitle><addtitle>J Neurol</addtitle><date>2009-03-01</date><risdate>2009</risdate><volume>256</volume><issue>3</issue><spage>493</spage><epage>498</epage><pages>493-498</pages><issn>0340-5354</issn><eissn>1432-1459</eissn><coden>JNRYA9</coden><abstract>Further to the wellestablished association between apolipoprotein E (APOE) and Alzheimer’s disease, this gene has also been implicated in both susceptibility to, and dementia in, Parkinson’s disease (PD). However studies to date have produced contradictory findings. We conducted a case-control study in a population of 528 PD patients and 512 healthy controls and found no significant difference in allele or genotype distribution of APOE between the two groups. An updated meta-analysis showed a modest increase of APOE-ε2 carriers amongst PD patients compared to controls [
P
= 0.017, OR = 1.16 (95 % CI 1.03–1.31)]. 107 of our patients were incident cases participating in a populationbased epidemiological study. Longitudinal follow-up of this cohort over a mean of 5.0 ± 0.7 years from diagnosis revealed no significant impact of APOE-ε4 carrier status on risk of dementia or rate of cognitive decline. An updated meta-analysis indicated an over-representation of APOE-ε4 carriers amongst PD dementia compared to non dementia cases [OR 1.74 (1.36–2.23),
P
= 1 × 10
–4
], although small sample sizes, heterogeneity of odds ratios and publication bias may have confounded this finding. In conclusion, our study does not support previously reported associations between APOE genotype and susceptibility to, or cognitive decline in, PD. An updated meta-analysis indicates any association with PD susceptibility is at most modest, an observation with important implications for further study of this issue. Large scale longitudinal studies would be best placed to further evaluate any impact of APOE genotype on cognitive decline in PD.</abstract><cop>Darmstadt</cop><pub>Steinkopff-Verlag</pub><pmid>19308307</pmid><doi>10.1007/s00415-009-0119-8</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-5354 |
| ispartof | Journal of neurology, 2009-03, Vol.256 (3), p.493-498 |
| issn | 0340-5354 1432-1459 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67195030 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Alzheimer's disease Apolipoprotein E2 - genetics Apolipoprotein E4 - genetics Apolipoproteins Apolipoproteins E - genetics Biological and medical sciences Case-Control Studies Cognition Disorders - complications Cognition Disorders - genetics Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dementia Dementia - complications Dementia - genetics Family medical history Female Follow-Up Studies Gene Frequency Genetic Predisposition to Disease Genotype & phenotype Health risk assessment Humans Longitudinal studies Male Medical sciences Medicine Medicine & Public Health Meta-analysis Middle Aged Neurology Neuropsychological Tests Neuroradiology Neurosciences Odds Ratio Original Communication Parkinson Disease - complications Parkinson Disease - genetics Parkinson's disease Risk Factors Sequence Analysis, DNA |
| title | Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s Disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T00%3A24%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Apolipoprotein%20E%20genotype%20as%20a%20risk%20factor%20for%20susceptibility%20to%20and%20dementia%20in%20Parkinson%E2%80%99s%20Disease&rft.jtitle=Journal%20of%20neurology&rft.au=Williams-Gray,%20C.%20H.&rft.date=2009-03-01&rft.volume=256&rft.issue=3&rft.spage=493&rft.epage=498&rft.pages=493-498&rft.issn=0340-5354&rft.eissn=1432-1459&rft.coden=JNRYA9&rft_id=info:doi/10.1007/s00415-009-0119-8&rft_dat=%3Cproquest_cross%3E1697511531%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=218151915&rft_id=info:pmid/19308307&rfr_iscdi=true |