IRGM variants and susceptibility to inflammatory bowel disease in the German population.
Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore ana...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3554777?pdf=render |
| _version_ | 1828736795803648000 |
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| author | Jürgen Glas Julia Seiderer Stephanie Bues Johannes Stallhofer Christoph Fries Torsten Olszak Eleni Tsekeri Martin Wetzke Florian Beigel Christian Steib Matthias Friedrich Burkhard Göke Julia Diegelmann Darina Czamara Stephan Brand |
| author_facet | Jürgen Glas Julia Seiderer Stephanie Bues Johannes Stallhofer Christoph Fries Torsten Olszak Eleni Tsekeri Martin Wetzke Florian Beigel Christian Steib Matthias Friedrich Burkhard Göke Julia Diegelmann Darina Czamara Stephan Brand |
| author_sort | Jürgen Glas |
| collection | DOAJ |
| description | Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study.Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin) was analyzed for six IRGM single nucleotide polymorphisms (SNPs) (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058). In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05-1.65]), rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06-1.66]) and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01-1.61]) with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (p<0.05). Genotype-phenotype analysis revealed no significant associations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes IRGM and ATG16L1 (p<0.05), which, however, did not remain significant after Bonferroni correction.Our results confirm IRGM as susceptibility gene for CD in the German population, supporting a role for the autophagy genes IRGM and ATG16L1 in the pathogenesis of CD. |
| first_indexed | 2024-04-12T23:31:38Z |
| format | Article |
| id | doaj.art-9f1e2b547fd04aa28e49b334a0a38979 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T23:31:38Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9f1e2b547fd04aa28e49b334a0a389792022-12-22T03:12:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5433810.1371/journal.pone.0054338IRGM variants and susceptibility to inflammatory bowel disease in the German population.Jürgen GlasJulia SeidererStephanie BuesJohannes StallhoferChristoph FriesTorsten OlszakEleni TsekeriMartin WetzkeFlorian BeigelChristian SteibMatthias FriedrichBurkhard GökeJulia DiegelmannDarina CzamaraStephan BrandGenome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study.Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin) was analyzed for six IRGM single nucleotide polymorphisms (SNPs) (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058). In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05-1.65]), rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06-1.66]) and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01-1.61]) with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (p<0.05). Genotype-phenotype analysis revealed no significant associations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes IRGM and ATG16L1 (p<0.05), which, however, did not remain significant after Bonferroni correction.Our results confirm IRGM as susceptibility gene for CD in the German population, supporting a role for the autophagy genes IRGM and ATG16L1 in the pathogenesis of CD.http://europepmc.org/articles/PMC3554777?pdf=render |
| spellingShingle | Jürgen Glas Julia Seiderer Stephanie Bues Johannes Stallhofer Christoph Fries Torsten Olszak Eleni Tsekeri Martin Wetzke Florian Beigel Christian Steib Matthias Friedrich Burkhard Göke Julia Diegelmann Darina Czamara Stephan Brand IRGM variants and susceptibility to inflammatory bowel disease in the German population. PLoS ONE |
| title | IRGM variants and susceptibility to inflammatory bowel disease in the German population. |
| title_full | IRGM variants and susceptibility to inflammatory bowel disease in the German population. |
| title_fullStr | IRGM variants and susceptibility to inflammatory bowel disease in the German population. |
| title_full_unstemmed | IRGM variants and susceptibility to inflammatory bowel disease in the German population. |
| title_short | IRGM variants and susceptibility to inflammatory bowel disease in the German population. |
| title_sort | irgm variants and susceptibility to inflammatory bowel disease in the german population |
| url | http://europepmc.org/articles/PMC3554777?pdf=render |
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