PTPN2 gene variants are associated with susceptibility to both Crohn's disease and ulcerative colitis supporting a common genetic disease background.
PTPN2 gene variants are associated with susceptibility to both Crohn's disease and ulcerative colitis supporting a common genetic disease background.
复制标题
DOI：
10.1371/journal.pone.0033682
复制
发表时间：
2012
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;Wagner J;Seiderer J;Olszak T;Wetzke M;Beigel F;Tillack C;Stallhofer J;Friedrich M;Steib C;Göke B;Ochsenkühn T;Karbalai N;Diegelmann J;Czamara D;Brand S
全基因组关联研究发现PTPN 2（蛋白酪氨酸磷酸酶，非受体2型）是炎症性肠病（IBD）的易感基因。然而，PTPN 2在克罗恩病（CD）和溃疡性结肠炎（UC）中的确切作用及其表型效应尚不清楚。因此，我们进行了详细的基因型-表型和上位性分析PTPN 2基因变异。分析了2131名高加索人（905名CD患者，318名UC患者和908名健康无关对照）的基因组DNA中PTPN 2区域的两个SNP（rs 2542151，rs7234029），在其他队列的既往研究中发现了与IBD的相关性。我们的分析显示PTPN 2 SNP rs 2542151与CD（p = 1.95×10−5; OR 1.49 [1.34-1.79]）和UC（p = 3.87×10−2，OR 1.31 [1.02-1.68]）的易感性显著相关。 此外，PTPN 2 SNP rs7234029与CD易感性显著相关（p = 1.30×10−3; OR 1.35 [1.13-1.62]），并有与UC相关的趋势（p = 7.53×10−2; OR 1.26 [0.98-1.62]）。 基因型-表型分析显示PTPN 2 SNP rs7234029与CD患者的狭窄疾病表型（B2）相关（p = 6.62×10−3）。 上位性分析显示CD中ATG 16 L1 SNP rs 2241879和PTPN 2 SNP rs 2542151之间存在弱上位性（p = 0.024），UC中ATG 16 L1 SNP rs 4663396和PTPN 2 SNP rs7234029之间存在弱上位性（p = 4.68×10−3）。 PTPN 2和NOD 2之间以及PTPN 2和IL 23 R之间没有上位性的证据。计算机模拟分析显示，SNP rs7234029可能调节炎症中涉及的几种转录因子的结合位点，包括加塔-3、NF-κB、C/EBP和E4 BP 4。我们的数据证实了PTPN 2变异体与CD和UC易感性的相关性，表明这些疾病的共同疾病病理机制。鉴于最近的证据表明PTPN 2调节肠上皮细胞中自噬体的形成，PTPN 2和ATG 16 L1之间的潜在联系应进一步研究。
Genome-wide association studies identified PTPN2 (protein tyrosine phosphatase, non-receptor type 2) as susceptibility gene for inflammatory bowel diseases (IBD). However, the exact role of PTPN2 in Crohn's disease (CD) and ulcerative colitis (UC) and its phenotypic effect are unclear. We therefore performed a detailed genotype-phenotype and epistasis analysis of PTPN2 gene variants. Genomic DNA from 2131 individuals of Caucasian origin (905 patients with CD, 318 patients with UC, and 908 healthy, unrelated controls) was analyzed for two SNPs in the PTPN2 region (rs2542151, rs7234029) for which associations with IBD were found in previous studies in other cohorts. Our analysis revealed a significant association of PTPN2 SNP rs2542151 with both susceptibility to CD (p = 1.95×10−5; OR 1.49 [1.34–1.79]) and UC (p = 3.87×10−2, OR 1.31 [1.02–1.68]). Moreover, PTPN2 SNP rs7234029 demonstrated a significant association with susceptibility to CD (p = 1.30×10−3; OR 1.35 [1.13–1.62]) and a trend towards association with UC (p = 7.53×10−2; OR 1.26 [0.98–1.62]). Genotype-phenotype analysis revealed an association of PTPN2 SNP rs7234029 with a stricturing disease phenotype (B2) in CD patients (p = 6.62×10−3). Epistasis analysis showed weak epistasis between the ATG16L1 SNP rs2241879 and PTPN2 SNP rs2542151 (p = 0.024) in CD and between ATG16L1 SNP rs4663396 and PTPN2 SNP rs7234029 (p = 4.68×10−3) in UC. There was no evidence of epistasis between PTPN2 and NOD2 and PTPN2 and IL23R. In silico analysis revealed that the SNP rs7234029 modulates potentially the binding sites of several transcription factors involved in inflammation including GATA-3, NF-κB, C/EBP, and E4BP4. Our data confirm the association of PTPN2 variants with susceptibility to both CD and UC, suggesting a common disease pathomechanism for these diseases. Given recent evidence that PTPN2 regulates autophagosome formation in intestinal epithelial cells, the potential link between PTPN2 and ATG16L1 should be further investigated.
登录
查看更多内容
影响因子：
4.5
作者：
Festen EA;Goyette P;Green T;Boucher G;Beauchamp C;Trynka G;Dubois PC;Lagacé C;Stokkers PC;Hommes DW;Barisani D;Palmieri O;Annese V;van Heel DA;Weersma RK;Daly MJ;Wijmenga C;Rioux JD
通讯作者：
Rioux JD
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：
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.