IRGM variants and susceptibility to inflammatory bowel disease in the German population.
IRGM variants and susceptibility to inflammatory bowel disease in the German population.
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DOI：
10.1371/journal.pone.0054338
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Brand S
中科院分区：
文献类型：
--
作者：
Glas J;Seiderer J;Bues S;Stallhofer J;Fries C;Olszak T;Tsekeri E;Wetzke M;Beigel F;Steib C;Friedrich M;Göke B;Diegelmann J;Czamara D;Brand S
全基因组关联研究发现，自噬基因IRGM与克罗恩病（CD）密切相关，但其在溃疡性结肠炎（UC）中的影响、其表型效应以及与其他IBD易感基因的潜在epistatic相互作用尚不清楚，因此我们在本研究中对其进行了分析。分析了2060例个体的基因组DNA，包括817例CD患者、283例UC患者和961例健康、非相关对照（均为高加索血统），检测了6个IRGM单核苷酸多态性（snp） （rs13371189, rs10065172 = p）。Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058)。对所有患者进行了详细的基因型-表型分析，并检测了三个主要CD易感基因NOD2、IL23R和ATG16L1的上位性。我们的分析显示IRGM snp 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]）和rs1000113 （p = 0.047, OR 1.27 [95% CI 1.01-1.61]）与CD易感性相关。这三个IRGM snp之间存在连锁不平衡。在UC中，几种IRGM单倍型与UC易感性呈弱相关（p<0.05）。基因型-表型分析显示与特定的IBD表型或回肠CD无显著关联。有证据表明，自噬基因IRGM和ATG16L1的几个snp之间存在弱的基因-基因相互作用（p<0.05），但经Bonferroni校正后，这种相互作用不显著。我们的研究结果证实IRGM是德国人群中CD的易感基因，支持自噬基因IRGM和ATG16L1在CD发病机制中的作用。
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.
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RS1004819是德国克罗恩病患者中与疾病相关的主要IL23R变体：IL23R，CARD15和OCTN1/2变体的联合分析。
影响因子：
3.7
作者：
Glas J;Seiderer J;Wetzke M;Konrad A;Török HP;Schmechel S;Tonenchi L;Grassl C;Dambacher J;Pfennig S;Maier K;Griga T;Klein W;Epplen JT;Schiemann U;Folwaczny C;Lohse P;Göke B;Ochsenkühn T;Müller-Myhsok B;Folwaczny M;Mussack T;Brand S
通讯作者：
Brand S
影响因子：
30.8
作者：
Fisher, Sheila A.;Tremelling, Mark;Anderson, Carl A.;Gwilliam, Rhian;Bumpstead, Suzannah;Prescott, Natalie J.;Nimmo, Elaine R.;Massey, Dunecan;Berzuini, Carlo;Johnson, Christopher;Barrett, Jeffrey C.;Cummings, Fraser R.;Drummond, Hazel;Lees, Charlie W.;Onnie, Clive M.;Hanson, Catherine E.;Blaszczyk, Katarzyna;Inouye, Mike;Ewels, Philip;Ravindrarajah, Radhi;Keniry, Andrew;Hunt, Sarah;Carter, Martyn;Watkins, Nick;Ouwehand, Willem;Lewis, Cathryn M.;Cardon, Lon;Lobo, Alan;Forbes, Alastair;Sanderson, Jeremy;Jewell, Derek P.;Mansfield, John C.;Deloukas, Panos;Mathew, Christopher G.;Parkes, Miles;Satsangi, Jack
通讯作者：
Satsangi, Jack
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Hampe, Jochen;Franke, Andre;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.