Expression and functional analysis of intestinal organic cation/l-carnitine transporter (OCTN) in Crohn's Disease
The IBD5 locus is a genetic risk factor for IBD, particularly Crohn's Disease, coding for the organic cation/carnitine transporters (OCTN1 and 2). Two variants of OCTN are associated with susceptibility to Crohn's Disease. Modified transport of carnitine in vitro has been reported for a po...
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| Veröffentlicht in: | Journal of Crohn's and colitis 2012-03, Vol.6 (2), p.189-197 |
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| container_title | Journal of Crohn's and colitis |
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| creator | Girardin, Marc Dionne, Serge Goyette, Philippe Rioux, John Bitton, Alain Elimrani, Ihsan Charlebois, Patrick Qureshi, Ijaz Levy, Emile Seidman, Ernest G. |
| description | The IBD5 locus is a genetic risk factor for IBD, particularly Crohn's Disease, coding for the organic cation/carnitine transporters (OCTN1 and 2). Two variants of OCTN are associated with susceptibility to Crohn's Disease. Modified transport of carnitine in vitro has been reported for a polymorphism of OCTN1. The aim was to investigate the function of intestinal OCTNs in IBD in relation to genetic polymorphisms.
Intestinal tissue was obtained from endoscopic biopsies and surgical resections from IBD patients (n=33 and 14, resp.) and controls (n=22 and 14, resp.). OCTN protein levels were measured in intestinal biopsies and carnitine transport was quantified in intestinal resections.
OCTN1 protein levels were significantly higher in ileal versus colonic tissue (2.95%±0.4 vs 0.66%±0.2, resp.; p |
| doi_str_mv | 10.1016/j.crohns.2011.08.003 |
| format | Article |
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Intestinal tissue was obtained from endoscopic biopsies and surgical resections from IBD patients (n=33 and 14, resp.) and controls (n=22 and 14, resp.). OCTN protein levels were measured in intestinal biopsies and carnitine transport was quantified in intestinal resections.
OCTN1 protein levels were significantly higher in ileal versus colonic tissue (2.95%±0.4 vs 0.66%±0.2, resp.; p<0.0002). OCTN1 expression was higher in Crohn's disease patients with mutant homozygous or heterozygous genotypes (0.6%±0.1 vs 3%±0.8, resp., p<0.02). Carnitine transport was very rapid and Na+ dependent (10s). It was not different comparing Crohn's Disease and control groups (0.45±0.12 vs 0.51±0.12nM carnitine/mg prot/min, resp.). Carnitine transport tended to be higher in subjects with mutant homozygous and heterozygous OCTN1 and OCTN2 genotypes (0.19 vs 0.59 and 0.25 vs 0.6, respectively).
The present data reveal that OCTN protein levels appear to be similar in intestinal tissue from Crohn's Disease patients and controls. Overall, ileal carnitine transport appears to as well equal in Crohn's Disease and control groups. However, there was a trend towards higher carnitine transport in subjects with OCTN1 and OCTN2 mutations.</description><identifier>ISSN: 1873-9946</identifier><identifier>EISSN: 1876-4479</identifier><identifier>DOI: 10.1016/j.crohns.2011.08.003</identifier><identifier>PMID: 22325173</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Adolescent ; Adult ; Aged ; Analysis of Variance ; Biological Transport - drug effects ; Biological Transport - genetics ; Carnitine ; Carnitine - pharmacokinetics ; Child ; Colitis, Ulcerative - genetics ; Colitis, Ulcerative - metabolism ; Colon - metabolism ; Crohn Disease - genetics ; Crohn Disease - metabolism ; Crohn's disease ; Female ; Genotype ; Heterozygote ; Homozygote ; Humans ; Ileum - metabolism ; Male ; Microvilli - metabolism ; Middle Aged ; Mutation ; Organic Cation Transport Proteins - genetics ; Organic Cation Transport Proteins - metabolism ; Organic cation/carnitine transporters ; Polymorphism, Genetic ; Sodium - pharmacology ; Solute Carrier Family 22 Member 5 ; Young Adult</subject><ispartof>Journal of Crohn's and colitis, 2012-03, Vol.6 (2), p.189-197</ispartof><rights>2011 European Crohn's and Colitis Organisation</rights><rights>Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-709af587d32653a11798db117c30e50c6629915a65f434ae74c3c507bfdb1d683</citedby><cites>FETCH-LOGICAL-c361t-709af587d32653a11798db117c30e50c6629915a65f434ae74c3c507bfdb1d683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22325173$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Girardin, Marc</creatorcontrib><creatorcontrib>Dionne, Serge</creatorcontrib><creatorcontrib>Goyette, Philippe</creatorcontrib><creatorcontrib>Rioux, John</creatorcontrib><creatorcontrib>Bitton, Alain</creatorcontrib><creatorcontrib>Elimrani, Ihsan</creatorcontrib><creatorcontrib>Charlebois, Patrick</creatorcontrib><creatorcontrib>Qureshi, Ijaz</creatorcontrib><creatorcontrib>Levy, Emile</creatorcontrib><creatorcontrib>Seidman, Ernest G.</creatorcontrib><title>Expression and functional analysis of intestinal organic cation/l-carnitine transporter (OCTN) in Crohn's Disease</title><title>Journal of Crohn's and colitis</title><addtitle>J Crohns Colitis</addtitle><description>The IBD5 locus is a genetic risk factor for IBD, particularly Crohn's Disease, coding for the organic cation/carnitine transporters (OCTN1 and 2). Two variants of OCTN are associated with susceptibility to Crohn's Disease. Modified transport of carnitine in vitro has been reported for a polymorphism of OCTN1. The aim was to investigate the function of intestinal OCTNs in IBD in relation to genetic polymorphisms.
Intestinal tissue was obtained from endoscopic biopsies and surgical resections from IBD patients (n=33 and 14, resp.) and controls (n=22 and 14, resp.). OCTN protein levels were measured in intestinal biopsies and carnitine transport was quantified in intestinal resections.
OCTN1 protein levels were significantly higher in ileal versus colonic tissue (2.95%±0.4 vs 0.66%±0.2, resp.; p<0.0002). OCTN1 expression was higher in Crohn's disease patients with mutant homozygous or heterozygous genotypes (0.6%±0.1 vs 3%±0.8, resp., p<0.02). Carnitine transport was very rapid and Na+ dependent (10s). It was not different comparing Crohn's Disease and control groups (0.45±0.12 vs 0.51±0.12nM carnitine/mg prot/min, resp.). Carnitine transport tended to be higher in subjects with mutant homozygous and heterozygous OCTN1 and OCTN2 genotypes (0.19 vs 0.59 and 0.25 vs 0.6, respectively).
The present data reveal that OCTN protein levels appear to be similar in intestinal tissue from Crohn's Disease patients and controls. Overall, ileal carnitine transport appears to as well equal in Crohn's Disease and control groups. However, there was a trend towards higher carnitine transport in subjects with OCTN1 and OCTN2 mutations.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis of Variance</subject><subject>Biological Transport - drug effects</subject><subject>Biological Transport - genetics</subject><subject>Carnitine</subject><subject>Carnitine - pharmacokinetics</subject><subject>Child</subject><subject>Colitis, Ulcerative - genetics</subject><subject>Colitis, Ulcerative - metabolism</subject><subject>Colon - metabolism</subject><subject>Crohn Disease - genetics</subject><subject>Crohn Disease - metabolism</subject><subject>Crohn's disease</subject><subject>Female</subject><subject>Genotype</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Ileum - metabolism</subject><subject>Male</subject><subject>Microvilli - metabolism</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Organic Cation Transport Proteins - genetics</subject><subject>Organic Cation Transport Proteins - metabolism</subject><subject>Organic cation/carnitine transporters</subject><subject>Polymorphism, Genetic</subject><subject>Sodium - pharmacology</subject><subject>Solute Carrier Family 22 Member 5</subject><subject>Young Adult</subject><issn>1873-9946</issn><issn>1876-4479</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtvGyEQgFHUqnn1H0QVtzSH3cCywHKpFLluU8lKLs4ZYXY2wVqzDrOu6n8fNnZ77GkY-ObBR8gVZyVnXN2uS5-Gl4hlxTgvWVMyJk7IGW-0Kupamw_vZ1EYU6tTco64ZkwaqZtP5LSqRCW5Fmfkdf5nmwAxDJG62NJuF_2YE9fn1PV7DEiHjoY4Ao5huh7Ss4vBU-8m7rYvvEsx5DegY3IRt0MaIdGvj7Plw00upLNpzWuk3wOCQ7gkHzvXI3w-xgvy9GO-nN0Xi8efv2Z3i8ILxcdCM-M62ehWVEoKx7k2TbvKwQsGknmlKmO4dEp2tagd6NoLL5ledZlqVSMuyPWh7zYNr7u8vd0E9ND3LsKwQ2sqXldCM57J-kBmoYgJOrtNYePS3nJmJ9d2bQ-u7eTassZm17nsy3HAbrWB9l_RX7kZ-HYAIH_zd4Bk0QeIHtqQwI-2HcL_J7wBSXySdw</recordid><startdate>201203</startdate><enddate>201203</enddate><creator>Girardin, Marc</creator><creator>Dionne, Serge</creator><creator>Goyette, Philippe</creator><creator>Rioux, John</creator><creator>Bitton, Alain</creator><creator>Elimrani, Ihsan</creator><creator>Charlebois, Patrick</creator><creator>Qureshi, Ijaz</creator><creator>Levy, Emile</creator><creator>Seidman, Ernest G.</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>201203</creationdate><title>Expression and functional analysis of intestinal organic cation/l-carnitine transporter (OCTN) in Crohn's Disease</title><author>Girardin, Marc ; Dionne, Serge ; Goyette, Philippe ; Rioux, John ; Bitton, Alain ; Elimrani, Ihsan ; Charlebois, Patrick ; Qureshi, Ijaz ; Levy, Emile ; Seidman, Ernest G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-709af587d32653a11798db117c30e50c6629915a65f434ae74c3c507bfdb1d683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Analysis of Variance</topic><topic>Biological Transport - drug effects</topic><topic>Biological Transport - genetics</topic><topic>Carnitine</topic><topic>Carnitine - pharmacokinetics</topic><topic>Child</topic><topic>Colitis, Ulcerative - genetics</topic><topic>Colitis, Ulcerative - metabolism</topic><topic>Colon - metabolism</topic><topic>Crohn Disease - genetics</topic><topic>Crohn Disease - metabolism</topic><topic>Crohn's disease</topic><topic>Female</topic><topic>Genotype</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Ileum - metabolism</topic><topic>Male</topic><topic>Microvilli - metabolism</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Organic Cation Transport Proteins - genetics</topic><topic>Organic Cation Transport Proteins - metabolism</topic><topic>Organic cation/carnitine transporters</topic><topic>Polymorphism, Genetic</topic><topic>Sodium - pharmacology</topic><topic>Solute Carrier Family 22 Member 5</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Girardin, Marc</creatorcontrib><creatorcontrib>Dionne, Serge</creatorcontrib><creatorcontrib>Goyette, Philippe</creatorcontrib><creatorcontrib>Rioux, John</creatorcontrib><creatorcontrib>Bitton, Alain</creatorcontrib><creatorcontrib>Elimrani, Ihsan</creatorcontrib><creatorcontrib>Charlebois, Patrick</creatorcontrib><creatorcontrib>Qureshi, Ijaz</creatorcontrib><creatorcontrib>Levy, Emile</creatorcontrib><creatorcontrib>Seidman, Ernest G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of Crohn's and colitis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Girardin, Marc</au><au>Dionne, Serge</au><au>Goyette, Philippe</au><au>Rioux, John</au><au>Bitton, Alain</au><au>Elimrani, Ihsan</au><au>Charlebois, Patrick</au><au>Qureshi, Ijaz</au><au>Levy, Emile</au><au>Seidman, Ernest G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression and functional analysis of intestinal organic cation/l-carnitine transporter (OCTN) in Crohn's Disease</atitle><jtitle>Journal of Crohn's and colitis</jtitle><addtitle>J Crohns Colitis</addtitle><date>2012-03</date><risdate>2012</risdate><volume>6</volume><issue>2</issue><spage>189</spage><epage>197</epage><pages>189-197</pages><issn>1873-9946</issn><eissn>1876-4479</eissn><abstract>The IBD5 locus is a genetic risk factor for IBD, particularly Crohn's Disease, coding for the organic cation/carnitine transporters (OCTN1 and 2). Two variants of OCTN are associated with susceptibility to Crohn's Disease. Modified transport of carnitine in vitro has been reported for a polymorphism of OCTN1. The aim was to investigate the function of intestinal OCTNs in IBD in relation to genetic polymorphisms.
Intestinal tissue was obtained from endoscopic biopsies and surgical resections from IBD patients (n=33 and 14, resp.) and controls (n=22 and 14, resp.). OCTN protein levels were measured in intestinal biopsies and carnitine transport was quantified in intestinal resections.
OCTN1 protein levels were significantly higher in ileal versus colonic tissue (2.95%±0.4 vs 0.66%±0.2, resp.; p<0.0002). OCTN1 expression was higher in Crohn's disease patients with mutant homozygous or heterozygous genotypes (0.6%±0.1 vs 3%±0.8, resp., p<0.02). Carnitine transport was very rapid and Na+ dependent (10s). It was not different comparing Crohn's Disease and control groups (0.45±0.12 vs 0.51±0.12nM carnitine/mg prot/min, resp.). Carnitine transport tended to be higher in subjects with mutant homozygous and heterozygous OCTN1 and OCTN2 genotypes (0.19 vs 0.59 and 0.25 vs 0.6, respectively).
The present data reveal that OCTN protein levels appear to be similar in intestinal tissue from Crohn's Disease patients and controls. Overall, ileal carnitine transport appears to as well equal in Crohn's Disease and control groups. However, there was a trend towards higher carnitine transport in subjects with OCTN1 and OCTN2 mutations.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>22325173</pmid><doi>10.1016/j.crohns.2011.08.003</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of Crohn's and colitis, 2012-03, Vol.6 (2), p.189-197 |
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| subjects | Adolescent Adult Aged Analysis of Variance Biological Transport - drug effects Biological Transport - genetics Carnitine Carnitine - pharmacokinetics Child Colitis, Ulcerative - genetics Colitis, Ulcerative - metabolism Colon - metabolism Crohn Disease - genetics Crohn Disease - metabolism Crohn's disease Female Genotype Heterozygote Homozygote Humans Ileum - metabolism Male Microvilli - metabolism Middle Aged Mutation Organic Cation Transport Proteins - genetics Organic Cation Transport Proteins - metabolism Organic cation/carnitine transporters Polymorphism, Genetic Sodium - pharmacology Solute Carrier Family 22 Member 5 Young Adult |
| title | Expression and functional analysis of intestinal organic cation/l-carnitine transporter (OCTN) in Crohn's Disease |
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