Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. The asso...
Gespeichert in:
| Veröffentlicht in: | PloS one 2022-04, Vol.17 (4), p.e0266590 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 4 |
| container_start_page | e0266590 |
| container_title | PloS one |
| container_volume | 17 |
| creator | Pronk, A C Seppala, L J Trajanoska, K Stringa, N van de Loo, B de Groot, L C P G M van Schoor, N M Koskeridis, F Markozannes, G Ntzani, E Uitterlinden, A G Rivadeneira, F Stricker, B H van der Velde, N |
| description | Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users.
The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated.
In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00).
This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention. |
| doi_str_mv | 10.1371/journal.pone.0266590 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2650244879</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A700446772</galeid><doaj_id>oai_doaj_org_article_087a3999bbd04522b59422609bc9139e</doaj_id><sourcerecordid>A700446772</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-8f8d1ca23dc0b4330d6a5a5dadede9c85d57cf959e191e0630803f618d09545a3</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QLguhFx3w0aXMjLIMfAwsLft2GtDntZMw0Y5Iu-u_NzHSXqeyFhJCQPO-bnJOcLHuO0QLTCr_buNEPyi52boAFIpwzgR5k51hQUnCC6MOT-Vn2JIQNQozWnD_OzigrCcalOM_kUg3aaBUh72GAaNr8RnmjhhjytJN6NBp2HkJI08KDTajOO2Vt7k34mZsh3xqtLRSqB33QOKvB50qPNoan2aPEBng2jRfZ948fvi0_F1fXn1bLy6ui5YLEou5qjVtFqG5RU1KKNFdMMa00aBBtzTSr2k4wAVhgQJyiGtGO41ojwUqm6EX28ui7sy7IKTdBEs4QKcu6EolYHQnt1EbuvNkq_0c6ZeRhwfleKp_ityBRXSkqhGgajUpGSMNESQhHomkFpgKS1_vptLHZgm5hiF7Zmel8ZzBr2bsbKRASFdpf5s1k4N2vEUKUWxNasFYN4MbDvXFKTEloQl_9g94f3UT1KgVghs6lc9u9qbysECpLXlUkUYt7qNQ0bE2bPlJn0vpM8HYmSEyE37FXYwhy9fXL_7PXP-bs6xN2DcrGdXB2jMYNYQ6WR7D1LgQP3V2SMZL7OrjNhtzXgZzqIMlenD7Qnej249O_A5cCAg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2650244879</pqid></control><display><type>article</type><title>Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Pronk, A C ; Seppala, L J ; Trajanoska, K ; Stringa, N ; van de Loo, B ; de Groot, L C P G M ; van Schoor, N M ; Koskeridis, F ; Markozannes, G ; Ntzani, E ; Uitterlinden, A G ; Rivadeneira, F ; Stricker, B H ; van der Velde, N</creator><contributor>Calafell, Francesc</contributor><creatorcontrib>Pronk, A C ; Seppala, L J ; Trajanoska, K ; Stringa, N ; van de Loo, B ; de Groot, L C P G M ; van Schoor, N M ; Koskeridis, F ; Markozannes, G ; Ntzani, E ; Uitterlinden, A G ; Rivadeneira, F ; Stricker, B H ; van der Velde, N ; Calafell, Francesc</creatorcontrib><description>Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users.
The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated.
In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00).
This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0266590</identifier><identifier>PMID: 35421149</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Aged ; Alleles ; Analysis ; Antidepressants ; Antidepressive Agents - adverse effects ; Biology and Life Sciences ; CYP2D6 protein ; Cytochrome P450 ; Drug dosages ; Epidemiology ; Falls ; Falls (Accidents) ; Gene polymorphism ; Genes ; Genetic aspects ; Genetic diversity ; Genetic polymorphisms ; Genetic variance ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genotype ; Geriatrics ; Haplotypes ; Health aspects ; Health risks ; Humans ; Hygiene ; Hypotension ; Injuries ; Internal medicine ; Medical ethics ; Medical research ; Medicine ; Medicine and Health Sciences ; Metabolism ; Middle Aged ; Older people ; Pharmacogenetics ; Pharmacokinetics ; Physiological aspects ; Polymorphism ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prospective Studies ; Public health ; Regression analysis ; Side effects</subject><ispartof>PloS one, 2022-04, Vol.17 (4), p.e0266590</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-8f8d1ca23dc0b4330d6a5a5dadede9c85d57cf959e191e0630803f618d09545a3</citedby><cites>FETCH-LOGICAL-c692t-8f8d1ca23dc0b4330d6a5a5dadede9c85d57cf959e191e0630803f618d09545a3</cites><orcidid>0000-0002-1253-7556 ; 0000-0001-5154-2369 ; 0000-0001-8481-579X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009709/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009709/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35421149$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Calafell, Francesc</contributor><creatorcontrib>Pronk, A C</creatorcontrib><creatorcontrib>Seppala, L J</creatorcontrib><creatorcontrib>Trajanoska, K</creatorcontrib><creatorcontrib>Stringa, N</creatorcontrib><creatorcontrib>van de Loo, B</creatorcontrib><creatorcontrib>de Groot, L C P G M</creatorcontrib><creatorcontrib>van Schoor, N M</creatorcontrib><creatorcontrib>Koskeridis, F</creatorcontrib><creatorcontrib>Markozannes, G</creatorcontrib><creatorcontrib>Ntzani, E</creatorcontrib><creatorcontrib>Uitterlinden, A G</creatorcontrib><creatorcontrib>Rivadeneira, F</creatorcontrib><creatorcontrib>Stricker, B H</creatorcontrib><creatorcontrib>van der Velde, N</creatorcontrib><title>Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users.
The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated.
In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00).
This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.</description><subject>Adults</subject><subject>Aged</subject><subject>Alleles</subject><subject>Analysis</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - adverse effects</subject><subject>Biology and Life Sciences</subject><subject>CYP2D6 protein</subject><subject>Cytochrome P450</subject><subject>Drug dosages</subject><subject>Epidemiology</subject><subject>Falls</subject><subject>Falls (Accidents)</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic polymorphisms</subject><subject>Genetic variance</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Geriatrics</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Humans</subject><subject>Hygiene</subject><subject>Hypotension</subject><subject>Injuries</subject><subject>Internal medicine</subject><subject>Medical ethics</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Older people</subject><subject>Pharmacogenetics</subject><subject>Pharmacokinetics</subject><subject>Physiological aspects</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prospective Studies</subject><subject>Public health</subject><subject>Regression analysis</subject><subject>Side effects</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLguhFx3w0aXMjLIMfAwsLft2GtDntZMw0Y5Iu-u_NzHSXqeyFhJCQPO-bnJOcLHuO0QLTCr_buNEPyi52boAFIpwzgR5k51hQUnCC6MOT-Vn2JIQNQozWnD_OzigrCcalOM_kUg3aaBUh72GAaNr8RnmjhhjytJN6NBp2HkJI08KDTajOO2Vt7k34mZsh3xqtLRSqB33QOKvB50qPNoan2aPEBng2jRfZ948fvi0_F1fXn1bLy6ui5YLEou5qjVtFqG5RU1KKNFdMMa00aBBtzTSr2k4wAVhgQJyiGtGO41ojwUqm6EX28ui7sy7IKTdBEs4QKcu6EolYHQnt1EbuvNkq_0c6ZeRhwfleKp_ityBRXSkqhGgajUpGSMNESQhHomkFpgKS1_vptLHZgm5hiF7Zmel8ZzBr2bsbKRASFdpf5s1k4N2vEUKUWxNasFYN4MbDvXFKTEloQl_9g94f3UT1KgVghs6lc9u9qbysECpLXlUkUYt7qNQ0bE2bPlJn0vpM8HYmSEyE37FXYwhy9fXL_7PXP-bs6xN2DcrGdXB2jMYNYQ6WR7D1LgQP3V2SMZL7OrjNhtzXgZzqIMlenD7Qnej249O_A5cCAg</recordid><startdate>20220414</startdate><enddate>20220414</enddate><creator>Pronk, A C</creator><creator>Seppala, L J</creator><creator>Trajanoska, K</creator><creator>Stringa, N</creator><creator>van de Loo, B</creator><creator>de Groot, L C P G M</creator><creator>van Schoor, N M</creator><creator>Koskeridis, F</creator><creator>Markozannes, G</creator><creator>Ntzani, E</creator><creator>Uitterlinden, A G</creator><creator>Rivadeneira, F</creator><creator>Stricker, B H</creator><creator>van der Velde, N</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1253-7556</orcidid><orcidid>https://orcid.org/0000-0001-5154-2369</orcidid><orcidid>https://orcid.org/0000-0001-8481-579X</orcidid></search><sort><creationdate>20220414</creationdate><title>Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults</title><author>Pronk, A C ; Seppala, L J ; Trajanoska, K ; Stringa, N ; van de Loo, B ; de Groot, L C P G M ; van Schoor, N M ; Koskeridis, F ; Markozannes, G ; Ntzani, E ; Uitterlinden, A G ; Rivadeneira, F ; Stricker, B H ; van der Velde, N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-8f8d1ca23dc0b4330d6a5a5dadede9c85d57cf959e191e0630803f618d09545a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adults</topic><topic>Aged</topic><topic>Alleles</topic><topic>Analysis</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - adverse effects</topic><topic>Biology and Life Sciences</topic><topic>CYP2D6 protein</topic><topic>Cytochrome P450</topic><topic>Drug dosages</topic><topic>Epidemiology</topic><topic>Falls</topic><topic>Falls (Accidents)</topic><topic>Gene polymorphism</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic polymorphisms</topic><topic>Genetic variance</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Geriatrics</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Health risks</topic><topic>Humans</topic><topic>Hygiene</topic><topic>Hypotension</topic><topic>Injuries</topic><topic>Internal medicine</topic><topic>Medical ethics</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Older people</topic><topic>Pharmacogenetics</topic><topic>Pharmacokinetics</topic><topic>Physiological aspects</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prospective Studies</topic><topic>Public health</topic><topic>Regression analysis</topic><topic>Side effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pronk, A C</creatorcontrib><creatorcontrib>Seppala, L J</creatorcontrib><creatorcontrib>Trajanoska, K</creatorcontrib><creatorcontrib>Stringa, N</creatorcontrib><creatorcontrib>van de Loo, B</creatorcontrib><creatorcontrib>de Groot, L C P G M</creatorcontrib><creatorcontrib>van Schoor, N M</creatorcontrib><creatorcontrib>Koskeridis, F</creatorcontrib><creatorcontrib>Markozannes, G</creatorcontrib><creatorcontrib>Ntzani, E</creatorcontrib><creatorcontrib>Uitterlinden, A G</creatorcontrib><creatorcontrib>Rivadeneira, F</creatorcontrib><creatorcontrib>Stricker, B H</creatorcontrib><creatorcontrib>van der Velde, N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pronk, A C</au><au>Seppala, L J</au><au>Trajanoska, K</au><au>Stringa, N</au><au>van de Loo, B</au><au>de Groot, L C P G M</au><au>van Schoor, N M</au><au>Koskeridis, F</au><au>Markozannes, G</au><au>Ntzani, E</au><au>Uitterlinden, A G</au><au>Rivadeneira, F</au><au>Stricker, B H</au><au>van der Velde, N</au><au>Calafell, Francesc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-04-14</date><risdate>2022</risdate><volume>17</volume><issue>4</issue><spage>e0266590</spage><pages>e0266590-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users.
The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated.
In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00).
This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35421149</pmid><doi>10.1371/journal.pone.0266590</doi><tpages>e0266590</tpages><orcidid>https://orcid.org/0000-0002-1253-7556</orcidid><orcidid>https://orcid.org/0000-0001-5154-2369</orcidid><orcidid>https://orcid.org/0000-0001-8481-579X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2022-04, Vol.17 (4), p.e0266590 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2650244879 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adults Aged Alleles Analysis Antidepressants Antidepressive Agents - adverse effects Biology and Life Sciences CYP2D6 protein Cytochrome P450 Drug dosages Epidemiology Falls Falls (Accidents) Gene polymorphism Genes Genetic aspects Genetic diversity Genetic polymorphisms Genetic variance Genome-wide association studies Genome-Wide Association Study Genomes Genotype Geriatrics Haplotypes Health aspects Health risks Humans Hygiene Hypotension Injuries Internal medicine Medical ethics Medical research Medicine Medicine and Health Sciences Metabolism Middle Aged Older people Pharmacogenetics Pharmacokinetics Physiological aspects Polymorphism Polymorphism, Genetic Polymorphism, Single Nucleotide Prospective Studies Public health Regression analysis Side effects |
| title | Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T19%3A34%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Candidate%20genetic%20variants%20and%20antidepressant-related%20fall%20risk%20in%20middle-aged%20and%20older%20adults&rft.jtitle=PloS%20one&rft.au=Pronk,%20A%20C&rft.date=2022-04-14&rft.volume=17&rft.issue=4&rft.spage=e0266590&rft.pages=e0266590-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0266590&rft_dat=%3Cgale_plos_%3EA700446772%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2650244879&rft_id=info:pmid/35421149&rft_galeid=A700446772&rft_doaj_id=oai_doaj_org_article_087a3999bbd04522b59422609bc9139e&rfr_iscdi=true |