Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease
Background and aims: The OCTN1 (SLC22A4 1672C→T) and OCTN2 (SLC22A5 −207G→C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease (CD), but their contribution in children has not been examined. Methods: These OCTN1/2 variants and IBD5 marker single n...
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| Veröffentlicht in: | Gut 2006-08, Vol.55 (8), p.1114-1123 |
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| description | Background and aims: The OCTN1 (SLC22A4 1672C→T) and OCTN2 (SLC22A5 −207G→C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease (CD), but their contribution in children has not been examined. Methods: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. Results: All SNPs were in strong linkage disequilibrium (D′ >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p |
| doi_str_mv | 10.1136/gut.2005.082107 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1856267</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>746127232</sourcerecordid><originalsourceid>FETCH-LOGICAL-b524t-d71a59962a51d11ca1238557dca75e25bd6598aa752675f12b6054d738781b343</originalsourceid><addsrcrecordid>eNqFkk1v1DAQhiMEotvCmRuyhEQlpOx6nPgjF6QSviqVlkNpuVlO4t31ksSL7XTJX-HX4u0u5eMAp5E9z7zj8bxJ8gTwFCBjs8UQpgRjOsWCAOb3kgnkTKQZEeJ-MsEYeEp5Xhwkh96vMMZCFPAwOQCWs4IX-ST5ftKrdvTGIztHYamR6eftoPtaby8uystzmBF0o5xRffBoY8LS9Lfg6avXFLW2HmJpjxrjtfIa-cHXeh1MZVoTRqT6Bi2c3YRlFG5MrX2MSCvXjrHK63DbT3WdCtaNqLIb3f7UepQ8mKvW68f7eJR8evvmsnyfnl28Oy1PztKKkjykDQdFi4IRRaEBqBWQTFDKm1pxqgmtGkYLoeKBME7nQCqGad7wTHABVZZnR8nLne56qDrd1LoPTrVy7Uyn3CitMvLPTG-WcmFvJAjKomYUON4LOPt10D7IzsRfaFvVazt4yXMGhJOMRPL5P0kmGIW4ogg--wtc2cHFVXkJnBdZRinGkZrtqNpZ752e3z0asNz6Q0Z_yK0_5M4fseLp77P-4veGiEC6A4wP-ttdXrkvMk7KqTy_KuX1h5KW1x-v5OfIv9jxVbf6b_cfS0LUPA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779335500</pqid></control><display><type>article</type><title>Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Russell, R K ; Drummond, H E ; Nimmo, E R ; Anderson, N H ; Noble, C L ; Wilson, D C ; Gillett, P M ; McGrogan, P ; Hassan, K ; Weaver, L T ; Bisset, W M ; Mahdi, G ; Satsangi, J</creator><creatorcontrib>Russell, R K ; Drummond, H E ; Nimmo, E R ; Anderson, N H ; Noble, C L ; Wilson, D C ; Gillett, P M ; McGrogan, P ; Hassan, K ; Weaver, L T ; Bisset, W M ; Mahdi, G ; Satsangi, J</creatorcontrib><description>Background and aims: The OCTN1 (SLC22A4 1672C→T) and OCTN2 (SLC22A5 −207G→C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease (CD), but their contribution in children has not been examined. Methods: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. Results: All SNPs were in strong linkage disequilibrium (D′ >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p = 0.02) and UC (28.2% v 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9th centile) at diagnosis (weight: 87.9% v 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4% (p<0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). Conclusions: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gut.2005.082107</identifier><identifier>PMID: 16469794</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Adolescent ; Adult ; Age ; Anthropometry ; Asthma ; Case-Control Studies ; Child ; Classification ; Colitis, Ulcerative - genetics ; Colitis, Ulcerative - pathology ; Colitis, Ulcerative - physiopathology ; Colon ; Crohn Disease - genetics ; Crohn Disease - pathology ; Crohn Disease - physiopathology ; Crohn's disease ; Cytokines ; Epistasis, Genetic ; Female ; Genes ; Genetic Predisposition to Disease ; Genomes ; Genotype ; Genotype & phenotype ; Growth ; Haplotypes ; Humans ; Hypersensitivity, Immediate - complications ; Hypersensitivity, Immediate - genetics ; IBD ; IBD5 ; indeterminate colitis ; Inflammatory Bowel Disease ; Inflammatory Bowel Diseases - genetics ; Inflammatory Bowel Diseases - pathology ; Inflammatory Bowel Diseases - physiopathology ; Linkage Disequilibrium ; Male ; Mutation ; OCTN ; Organic Cation Transport Proteins - genetics ; Patients ; Phenotype ; Polymorphism, Single Nucleotide ; single nucleotide polymorphism ; SNP ; Solute Carrier Family 22 Member 5 ; Studies ; ulcerative colitis</subject><ispartof>Gut, 2006-08, Vol.55 (8), p.1114-1123</ispartof><rights>Copyright 2006 by Gut</rights><rights>Copyright: 2006 Copyright 2006 by Gut</rights><rights>Copyright © 2006 BMJ Publishing Group & British Society of Gastroenterology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b524t-d71a59962a51d11ca1238557dca75e25bd6598aa752675f12b6054d738781b343</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://gut.bmj.com/content/55/8/1114.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://gut.bmj.com/content/55/8/1114.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,723,776,780,881,3183,23550,27901,27902,53766,53768,77342,77373</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16469794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Russell, R K</creatorcontrib><creatorcontrib>Drummond, H E</creatorcontrib><creatorcontrib>Nimmo, E R</creatorcontrib><creatorcontrib>Anderson, N H</creatorcontrib><creatorcontrib>Noble, C L</creatorcontrib><creatorcontrib>Wilson, D C</creatorcontrib><creatorcontrib>Gillett, P M</creatorcontrib><creatorcontrib>McGrogan, P</creatorcontrib><creatorcontrib>Hassan, K</creatorcontrib><creatorcontrib>Weaver, L T</creatorcontrib><creatorcontrib>Bisset, W M</creatorcontrib><creatorcontrib>Mahdi, G</creatorcontrib><creatorcontrib>Satsangi, J</creatorcontrib><title>Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease</title><title>Gut</title><addtitle>Gut</addtitle><description>Background and aims: The OCTN1 (SLC22A4 1672C→T) and OCTN2 (SLC22A5 −207G→C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease (CD), but their contribution in children has not been examined. Methods: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. Results: All SNPs were in strong linkage disequilibrium (D′ >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p = 0.02) and UC (28.2% v 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9th centile) at diagnosis (weight: 87.9% v 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4% (p<0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). Conclusions: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Anthropometry</subject><subject>Asthma</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Classification</subject><subject>Colitis, Ulcerative - genetics</subject><subject>Colitis, Ulcerative - pathology</subject><subject>Colitis, Ulcerative - physiopathology</subject><subject>Colon</subject><subject>Crohn Disease - genetics</subject><subject>Crohn Disease - pathology</subject><subject>Crohn Disease - physiopathology</subject><subject>Crohn's disease</subject><subject>Cytokines</subject><subject>Epistasis, Genetic</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Growth</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Hypersensitivity, Immediate - complications</subject><subject>Hypersensitivity, Immediate - genetics</subject><subject>IBD</subject><subject>IBD5</subject><subject>indeterminate colitis</subject><subject>Inflammatory Bowel Disease</subject><subject>Inflammatory Bowel Diseases - genetics</subject><subject>Inflammatory Bowel Diseases - pathology</subject><subject>Inflammatory Bowel Diseases - physiopathology</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Mutation</subject><subject>OCTN</subject><subject>Organic Cation Transport Proteins - genetics</subject><subject>Patients</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>single nucleotide polymorphism</subject><subject>SNP</subject><subject>Solute Carrier Family 22 Member 5</subject><subject>Studies</subject><subject>ulcerative colitis</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkk1v1DAQhiMEotvCmRuyhEQlpOx6nPgjF6QSviqVlkNpuVlO4t31ksSL7XTJX-HX4u0u5eMAp5E9z7zj8bxJ8gTwFCBjs8UQpgRjOsWCAOb3kgnkTKQZEeJ-MsEYeEp5Xhwkh96vMMZCFPAwOQCWs4IX-ST5ftKrdvTGIztHYamR6eftoPtaby8uystzmBF0o5xRffBoY8LS9Lfg6avXFLW2HmJpjxrjtfIa-cHXeh1MZVoTRqT6Bi2c3YRlFG5MrX2MSCvXjrHK63DbT3WdCtaNqLIb3f7UepQ8mKvW68f7eJR8evvmsnyfnl28Oy1PztKKkjykDQdFi4IRRaEBqBWQTFDKm1pxqgmtGkYLoeKBME7nQCqGad7wTHABVZZnR8nLne56qDrd1LoPTrVy7Uyn3CitMvLPTG-WcmFvJAjKomYUON4LOPt10D7IzsRfaFvVazt4yXMGhJOMRPL5P0kmGIW4ogg--wtc2cHFVXkJnBdZRinGkZrtqNpZ752e3z0asNz6Q0Z_yK0_5M4fseLp77P-4veGiEC6A4wP-ttdXrkvMk7KqTy_KuX1h5KW1x-v5OfIv9jxVbf6b_cfS0LUPA</recordid><startdate>20060801</startdate><enddate>20060801</enddate><creator>Russell, R K</creator><creator>Drummond, H E</creator><creator>Nimmo, E R</creator><creator>Anderson, N H</creator><creator>Noble, C L</creator><creator>Wilson, D C</creator><creator>Gillett, P M</creator><creator>McGrogan, P</creator><creator>Hassan, K</creator><creator>Weaver, L T</creator><creator>Bisset, W M</creator><creator>Mahdi, G</creator><creator>Satsangi, J</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20060801</creationdate><title>Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease</title><author>Russell, R K ; Drummond, H E ; Nimmo, E R ; Anderson, N H ; Noble, C L ; Wilson, D C ; Gillett, P M ; McGrogan, P ; Hassan, K ; Weaver, L T ; Bisset, W M ; Mahdi, G ; Satsangi, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b524t-d71a59962a51d11ca1238557dca75e25bd6598aa752675f12b6054d738781b343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Anthropometry</topic><topic>Asthma</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Classification</topic><topic>Colitis, Ulcerative - genetics</topic><topic>Colitis, Ulcerative - pathology</topic><topic>Colitis, Ulcerative - physiopathology</topic><topic>Colon</topic><topic>Crohn Disease - genetics</topic><topic>Crohn Disease - pathology</topic><topic>Crohn Disease - physiopathology</topic><topic>Crohn's disease</topic><topic>Cytokines</topic><topic>Epistasis, Genetic</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic Predisposition to Disease</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Growth</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Hypersensitivity, Immediate - complications</topic><topic>Hypersensitivity, Immediate - genetics</topic><topic>IBD</topic><topic>IBD5</topic><topic>indeterminate colitis</topic><topic>Inflammatory Bowel Disease</topic><topic>Inflammatory Bowel Diseases - genetics</topic><topic>Inflammatory Bowel Diseases - pathology</topic><topic>Inflammatory Bowel Diseases - physiopathology</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Mutation</topic><topic>OCTN</topic><topic>Organic Cation Transport Proteins - genetics</topic><topic>Patients</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>single nucleotide polymorphism</topic><topic>SNP</topic><topic>Solute Carrier Family 22 Member 5</topic><topic>Studies</topic><topic>ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Russell, R K</creatorcontrib><creatorcontrib>Drummond, H E</creatorcontrib><creatorcontrib>Nimmo, E R</creatorcontrib><creatorcontrib>Anderson, N H</creatorcontrib><creatorcontrib>Noble, C L</creatorcontrib><creatorcontrib>Wilson, D C</creatorcontrib><creatorcontrib>Gillett, P M</creatorcontrib><creatorcontrib>McGrogan, P</creatorcontrib><creatorcontrib>Hassan, K</creatorcontrib><creatorcontrib>Weaver, L T</creatorcontrib><creatorcontrib>Bisset, W M</creatorcontrib><creatorcontrib>Mahdi, G</creatorcontrib><creatorcontrib>Satsangi, J</creatorcontrib><collection>Istex</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science 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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Russell, R K</au><au>Drummond, H E</au><au>Nimmo, E R</au><au>Anderson, N H</au><au>Noble, C L</au><au>Wilson, D C</au><au>Gillett, P M</au><au>McGrogan, P</au><au>Hassan, K</au><au>Weaver, L T</au><au>Bisset, W M</au><au>Mahdi, G</au><au>Satsangi, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2006-08-01</date><risdate>2006</risdate><volume>55</volume><issue>8</issue><spage>1114</spage><epage>1123</epage><pages>1114-1123</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><coden>GUTTAK</coden><abstract>Background and aims: The OCTN1 (SLC22A4 1672C→T) and OCTN2 (SLC22A5 −207G→C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease (CD), but their contribution in children has not been examined. Methods: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. Results: All SNPs were in strong linkage disequilibrium (D′ >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p = 0.02) and UC (28.2% v 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9th centile) at diagnosis (weight: 87.9% v 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4% (p<0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). Conclusions: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.</abstract><cop>England</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>16469794</pmid><doi>10.1136/gut.2005.082107</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Gut, 2006-08, Vol.55 (8), p.1114-1123 |
| issn | 0017-5749 1468-3288 |
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| source | MEDLINE; BMJ Journals - NESLi2; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adolescent Adult Age Anthropometry Asthma Case-Control Studies Child Classification Colitis, Ulcerative - genetics Colitis, Ulcerative - pathology Colitis, Ulcerative - physiopathology Colon Crohn Disease - genetics Crohn Disease - pathology Crohn Disease - physiopathology Crohn's disease Cytokines Epistasis, Genetic Female Genes Genetic Predisposition to Disease Genomes Genotype Genotype & phenotype Growth Haplotypes Humans Hypersensitivity, Immediate - complications Hypersensitivity, Immediate - genetics IBD IBD5 indeterminate colitis Inflammatory Bowel Disease Inflammatory Bowel Diseases - genetics Inflammatory Bowel Diseases - pathology Inflammatory Bowel Diseases - physiopathology Linkage Disequilibrium Male Mutation OCTN Organic Cation Transport Proteins - genetics Patients Phenotype Polymorphism, Single Nucleotide single nucleotide polymorphism SNP Solute Carrier Family 22 Member 5 Studies ulcerative colitis |
| title | Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T03%3A38%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Analysis%20of%20the%20influence%20of%20OCTN1/2%20variants%20within%20the%20IBD5%20locus%20on%20disease%20susceptibility%20and%20growth%20indices%20in%20early%20onset%20inflammatory%20bowel%20disease&rft.jtitle=Gut&rft.au=Russell,%20R%20K&rft.date=2006-08-01&rft.volume=55&rft.issue=8&rft.spage=1114&rft.epage=1123&rft.pages=1114-1123&rft.issn=0017-5749&rft.eissn=1468-3288&rft.coden=GUTTAK&rft_id=info:doi/10.1136/gut.2005.082107&rft_dat=%3Cproquest_pubme%3E746127232%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1779335500&rft_id=info:pmid/16469794&rfr_iscdi=true |