Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study.

Hdl Handle:
http://hdl.handle.net/10147/107722
Title:
Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study.
Authors:
Brophy, Karen; Ryan, Anthony W; Turner, Graham; Trimble, Valerie; Patel, Kunal D; O'Morain, Colm; Kennedy, Nicholas P; Egan, Brian; Close, Eimear; Lawlor, Garrett; MacMathuna, Padraic; Stevens, Fiona M; Abuzakouk, Mohamed; Feighery, Conleth; Kelleher, Dermot; McManus, Ross
Affiliation:
Department of Clinical Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St James's Hospital, Dublin, Ireland.
Citation:
Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study. 2010, 11:76 BMC Med. Genet.
Journal:
BMC medical genetics
Issue Date:
2010
URI:
http://hdl.handle.net/10147/107722
DOI:
10.1186/1471-2350-11-76
PubMed ID:
20478055
Abstract:
BACKGROUND: Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. METHODS: We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. RESULTS: Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. CONCLUSION: Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine's role in maintaining inflammation in active CD.
Language:
en
MeSH:
Case-Control Studies; Celiac Disease; Chromosome Mapping; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 5; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Interleukin-10; Interleukin-10 Receptor alpha Subunit; Interleukin-18; Linkage (Genetics); Polymorphism, Single Nucleotide; Risk; Risk Factors
ISSN:
1471-2350

Full metadata record

DC FieldValue Language
dc.contributor.authorBrophy, Karenen
dc.contributor.authorRyan, Anthony Wen
dc.contributor.authorTurner, Grahamen
dc.contributor.authorTrimble, Valerieen
dc.contributor.authorPatel, Kunal Den
dc.contributor.authorO'Morain, Colmen
dc.contributor.authorKennedy, Nicholas Pen
dc.contributor.authorEgan, Brianen
dc.contributor.authorClose, Eimearen
dc.contributor.authorLawlor, Garretten
dc.contributor.authorMacMathuna, Padraicen
dc.contributor.authorStevens, Fiona Men
dc.contributor.authorAbuzakouk, Mohameden
dc.contributor.authorFeighery, Conlethen
dc.contributor.authorKelleher, Dermoten
dc.contributor.authorMcManus, Rossen
dc.date.accessioned2010-07-15T12:40:17Z-
dc.date.available2010-07-15T12:40:17Z-
dc.date.issued2010-
dc.identifier.citationEvaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study. 2010, 11:76 BMC Med. Genet.en
dc.identifier.issn1471-2350-
dc.identifier.pmid20478055-
dc.identifier.doi10.1186/1471-2350-11-76-
dc.identifier.urihttp://hdl.handle.net/10147/107722-
dc.description.abstractBACKGROUND: Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. METHODS: We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. RESULTS: Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. CONCLUSION: Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine's role in maintaining inflammation in active CD.-
dc.language.isoenen
dc.subject.meshCase-Control Studies-
dc.subject.meshCeliac Disease-
dc.subject.meshChromosome Mapping-
dc.subject.meshChromosomes, Human, Pair 11-
dc.subject.meshChromosomes, Human, Pair 5-
dc.subject.meshGenetic Association Studies-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenetic Variation-
dc.subject.meshHumans-
dc.subject.meshInterleukin-10-
dc.subject.meshInterleukin-10 Receptor alpha Subunit-
dc.subject.meshInterleukin-18-
dc.subject.meshLinkage (Genetics)-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshRisk-
dc.subject.meshRisk Factors-
dc.titleEvaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study.en
dc.contributor.departmentDepartment of Clinical Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St James's Hospital, Dublin, Ireland.en
dc.identifier.journalBMC medical geneticsen

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.