Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis
Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these varia...
Gespeichert in:
| Veröffentlicht in: | PloS one 2018-03, Vol.13 (3), p.e0192806-e0192806 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0192806 |
|---|---|
| container_issue | 3 |
| container_start_page | e0192806 |
| container_title | PloS one |
| container_volume | 13 |
| creator | Moran, Christopher J Huang, Hailiang Rivas, Manuel Kaplan, Jess L Daly, Mark J Winter, Harland S |
| description | Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC.
Subjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001).
457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5).
Common transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome. |
| doi_str_mv | 10.1371/journal.pone.0192806 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2018658168</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A532339411</galeid><doaj_id>oai_doaj_org_article_94172b5083cd4090a7190c8e16d1e36e</doaj_id><sourcerecordid>A532339411</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-13c50f77a07a27dada49caee903c9614c21b79ef76d58a512f93026ff956ea0e3</originalsourceid><addsrcrecordid>eNqNk12LEzEUhgdR3HX1H4gOCKIXrfmYyUxuhGXRtbCw4Nel4TRzpk1Jk26SKfrvTbfdpSN7IXORIXnOe3LenFMULymZUt7QDys_BAd2uvEOp4RK1hLxqDilkrOJYIQ_Pvo_KZ7FuCKk5q0QT4sTJutGkoqdFr8u0WEyutxCMOBSLI0rNVo7WAhlCuDixodUdr50PpXQ96hTucYIFtbGYRkwAy7iLm6wGgMks8VSe2uSic-LJz3YiC8O61nx4_On7xdfJlfXl7OL86uJFpKlCeW6Jn3TAGmANR10UEkNiJJwLQWtNKPzRmLfiK5uoaasl5ww0feyFggE-Vnxeq-7sT6qgzVRMUJbUbdUtJmY7YnOw0ptgllD-KM8GHW74cNCQchGWFSyog2b16TluquIJNBQSXSLVHQUudhl-3jINszX2Gl02Sg7Eh2fOLNUC79VdSvaRvAs8O4gEPzNgDGptYk718GhH27vnZ-Htpxk9M0_6MPVHagF5AKM633Oq3ei6rzmjPNcE83U9AEqfx2ujc591Ju8Pwp4PwrITMLfaQFDjGr27ev_s9c_x-zbI3aJYNMyejskk1tpDFZ7UAcfY8D-3mRK1G4M7txQuzFQhzHIYa-OH-g-6K7v-V_oQQJt</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2018658168</pqid></control><display><type>article</type><title>Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis</title><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Moran, Christopher J ; Huang, Hailiang ; Rivas, Manuel ; Kaplan, Jess L ; Daly, Mark J ; Winter, Harland S</creator><contributor>Bandapalli, Obul Reddy</contributor><creatorcontrib>Moran, Christopher J ; Huang, Hailiang ; Rivas, Manuel ; Kaplan, Jess L ; Daly, Mark J ; Winter, Harland S ; Bandapalli, Obul Reddy</creatorcontrib><description>Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC.
Subjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001).
457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5).
Common transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0192806</identifier><identifier>PMID: 29579042</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adults ; Biology and Life Sciences ; Care and treatment ; Colon ; Development and progression ; Engineering and Technology ; Environmental factors ; Gastroenterology ; Gene expression ; Gene frequency ; Genes ; Genetic aspects ; Genetic diversity ; Genetic variance ; Genetic variation ; Genetics ; Genomes ; Genotyping ; Health aspects ; Hepatology ; Hospitals ; Inflammatory bowel disease ; Intestine ; Medicine and Health Sciences ; Mesalamine ; Microbiomes ; Mucosa ; Nutrition ; Patient outcomes ; Pediatrics ; Proteins ; Quality control ; Research and Analysis Methods ; Single-nucleotide polymorphism ; Transport ; Tumor necrosis factor-TNF ; Ulcerative colitis</subject><ispartof>PloS one, 2018-03, Vol.13 (3), p.e0192806-e0192806</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Moran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Moran et al 2018 Moran et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-13c50f77a07a27dada49caee903c9614c21b79ef76d58a512f93026ff956ea0e3</citedby><cites>FETCH-LOGICAL-c692t-13c50f77a07a27dada49caee903c9614c21b79ef76d58a512f93026ff956ea0e3</cites><orcidid>0000-0003-1966-3499</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/PMC5868763/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868763/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29579042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bandapalli, Obul Reddy</contributor><creatorcontrib>Moran, Christopher J</creatorcontrib><creatorcontrib>Huang, Hailiang</creatorcontrib><creatorcontrib>Rivas, Manuel</creatorcontrib><creatorcontrib>Kaplan, Jess L</creatorcontrib><creatorcontrib>Daly, Mark J</creatorcontrib><creatorcontrib>Winter, Harland S</creatorcontrib><title>Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC.
Subjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001).
457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5).
Common transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome.</description><subject>Acids</subject><subject>Adults</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>Colon</subject><subject>Development and progression</subject><subject>Engineering and Technology</subject><subject>Environmental factors</subject><subject>Gastroenterology</subject><subject>Gene expression</subject><subject>Gene frequency</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic variance</subject><subject>Genetic variation</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Health aspects</subject><subject>Hepatology</subject><subject>Hospitals</subject><subject>Inflammatory bowel disease</subject><subject>Intestine</subject><subject>Medicine and Health Sciences</subject><subject>Mesalamine</subject><subject>Microbiomes</subject><subject>Mucosa</subject><subject>Nutrition</subject><subject>Patient outcomes</subject><subject>Pediatrics</subject><subject>Proteins</subject><subject>Quality control</subject><subject>Research and Analysis Methods</subject><subject>Single-nucleotide polymorphism</subject><subject>Transport</subject><subject>Tumor necrosis factor-TNF</subject><subject>Ulcerative colitis</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><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>eNqNk12LEzEUhgdR3HX1H4gOCKIXrfmYyUxuhGXRtbCw4Nel4TRzpk1Jk26SKfrvTbfdpSN7IXORIXnOe3LenFMULymZUt7QDys_BAd2uvEOp4RK1hLxqDilkrOJYIQ_Pvo_KZ7FuCKk5q0QT4sTJutGkoqdFr8u0WEyutxCMOBSLI0rNVo7WAhlCuDixodUdr50PpXQ96hTucYIFtbGYRkwAy7iLm6wGgMks8VSe2uSic-LJz3YiC8O61nx4_On7xdfJlfXl7OL86uJFpKlCeW6Jn3TAGmANR10UEkNiJJwLQWtNKPzRmLfiK5uoaasl5ww0feyFggE-Vnxeq-7sT6qgzVRMUJbUbdUtJmY7YnOw0ptgllD-KM8GHW74cNCQchGWFSyog2b16TluquIJNBQSXSLVHQUudhl-3jINszX2Gl02Sg7Eh2fOLNUC79VdSvaRvAs8O4gEPzNgDGptYk718GhH27vnZ-Htpxk9M0_6MPVHagF5AKM633Oq3ei6rzmjPNcE83U9AEqfx2ujc591Ju8Pwp4PwrITMLfaQFDjGr27ev_s9c_x-zbI3aJYNMyejskk1tpDFZ7UAcfY8D-3mRK1G4M7txQuzFQhzHIYa-OH-g-6K7v-V_oQQJt</recordid><startdate>20180326</startdate><enddate>20180326</enddate><creator>Moran, Christopher J</creator><creator>Huang, Hailiang</creator><creator>Rivas, Manuel</creator><creator>Kaplan, Jess L</creator><creator>Daly, Mark J</creator><creator>Winter, Harland S</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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/0000-0003-1966-3499</orcidid></search><sort><creationdate>20180326</creationdate><title>Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis</title><author>Moran, Christopher J ; Huang, Hailiang ; Rivas, Manuel ; Kaplan, Jess L ; Daly, Mark J ; Winter, Harland S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-13c50f77a07a27dada49caee903c9614c21b79ef76d58a512f93026ff956ea0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acids</topic><topic>Adults</topic><topic>Biology and Life Sciences</topic><topic>Care and treatment</topic><topic>Colon</topic><topic>Development and progression</topic><topic>Engineering and Technology</topic><topic>Environmental factors</topic><topic>Gastroenterology</topic><topic>Gene expression</topic><topic>Gene frequency</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic variance</topic><topic>Genetic variation</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Genotyping</topic><topic>Health aspects</topic><topic>Hepatology</topic><topic>Hospitals</topic><topic>Inflammatory bowel disease</topic><topic>Intestine</topic><topic>Medicine and Health Sciences</topic><topic>Mesalamine</topic><topic>Microbiomes</topic><topic>Mucosa</topic><topic>Nutrition</topic><topic>Patient outcomes</topic><topic>Pediatrics</topic><topic>Proteins</topic><topic>Quality control</topic><topic>Research and Analysis Methods</topic><topic>Single-nucleotide polymorphism</topic><topic>Transport</topic><topic>Tumor necrosis factor-TNF</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moran, Christopher J</creatorcontrib><creatorcontrib>Huang, Hailiang</creatorcontrib><creatorcontrib>Rivas, Manuel</creatorcontrib><creatorcontrib>Kaplan, Jess L</creatorcontrib><creatorcontrib>Daly, Mark J</creatorcontrib><creatorcontrib>Winter, Harland S</creatorcontrib><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>Moran, Christopher J</au><au>Huang, Hailiang</au><au>Rivas, Manuel</au><au>Kaplan, Jess L</au><au>Daly, Mark J</au><au>Winter, Harland S</au><au>Bandapalli, Obul Reddy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-03-26</date><risdate>2018</risdate><volume>13</volume><issue>3</issue><spage>e0192806</spage><epage>e0192806</epage><pages>e0192806-e0192806</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC.
Subjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001).
457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5).
Common transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29579042</pmid><doi>10.1371/journal.pone.0192806</doi><tpages>e0192806</tpages><orcidid>https://orcid.org/0000-0003-1966-3499</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-03, Vol.13 (3), p.e0192806-e0192806 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2018658168 |
| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Adults Biology and Life Sciences Care and treatment Colon Development and progression Engineering and Technology Environmental factors Gastroenterology Gene expression Gene frequency Genes Genetic aspects Genetic diversity Genetic variance Genetic variation Genetics Genomes Genotyping Health aspects Hepatology Hospitals Inflammatory bowel disease Intestine Medicine and Health Sciences Mesalamine Microbiomes Mucosa Nutrition Patient outcomes Pediatrics Proteins Quality control Research and Analysis Methods Single-nucleotide polymorphism Transport Tumor necrosis factor-TNF Ulcerative colitis |
| title | Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T11%3A18%3A55IST&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=Genetic%20variants%20in%20cellular%20transport%20do%20not%20affect%20mesalamine%20response%20in%20ulcerative%20colitis&rft.jtitle=PloS%20one&rft.au=Moran,%20Christopher%20J&rft.date=2018-03-26&rft.volume=13&rft.issue=3&rft.spage=e0192806&rft.epage=e0192806&rft.pages=e0192806-e0192806&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0192806&rft_dat=%3Cgale_plos_%3EA532339411%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=2018658168&rft_id=info:pmid/29579042&rft_galeid=A532339411&rft_doaj_id=oai_doaj_org_article_94172b5083cd4090a7190c8e16d1e36e&rfr_iscdi=true |