Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis.
Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis.
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DOI：
10.1002/ibd.21579
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发表时间：
2011-09
影响因子：
4.9
通讯作者：
Silverberg, Mark S.
中科院分区：
文献类型：
--
作者：
Waterman, Matti;Xu, Wei;Stempak, Joanne M.;Milgrom, Raquel;Bernstein, Charles N.;Griffiths, Anne M.;Greenberg, Gordon R.;Steinhart, A. Hillary;Silverberg, Mark S.
溃疡性结肠炎（UC）和克罗恩病（CD）的共同基因型基础是由重叠的临床特征、流行病学研究和与UC和CD相关的基因所暗示的。我们评估了CD和UC基因位点之间的重叠，这些基因位点按发病途径和疾病位置分层。在加拿大IBD队列（n = 2374）中测定了6个uc相关和34个cd相关单核苷酸多态性（snp）的等位基因频率。对乳糜泻、UC、单结肠乳糜泻、回肠乳糜泻和对照组的差异进行分析，以控制种族、诊断年龄和性别。总的来说，34个CD相关snp中有21个在UC （n = 1230）和CD （n = 1144）中具有相似的等位基因频率。6个uc相关snp中有3个在CD中具有显著不同的频率（n = 1144）。CD和UC之间的等位基因频率差异主要出现在NOD2/自噬途径的snp中，而频率相似的snp主要出现在IL-22/23、Th17、适应性免疫和屏障途径中。仅结肠型CD （n = 228）与健康对照比较：6个UC snp中的3个（MST1、HLA-DRA和IL-23R）和34个CD snp中的11个（IRGM、NOD2 （rs2066845）、CCNY、MST1、IL23R、PTPN22、C11orf30、ZNF365、PTPN2、PSMG1和rs1456893）显著相关。总的来说，34个CD snp中有29个在结肠CD中具有与回肠CD相似的等位基因频率（n = 366）。所有UC snp在UC和结肠CD中具有相似的频率。我们的研究结果表明，CD和UC具有与适应性免疫受损相关的共同遗传关联，并且在外源抗原处理途径上存在分歧。单结肠型乳糜泻与UC有广泛的重叠，与回肠型乳糜泻也有相当大的重叠。
A common genotypic basis for ulcerative colitis (UC) and Crohn's disease (CD) is implied by overlapping clinical characteristics, epidemiological studies, and association of genes with both UC and CD. We evaluated the overlap between CD and UC genetic loci stratified by pathogenetic pathways and by disease location. The allele frequencies of six UC-associated and 34 CD-associated single nucleotide polymorphisms (SNPs) were determined in a Canadian IBD cohort (n = 2374). Differences between CD, UC, colon-only CD, ileal CD, and controls were analyzed controlling for ethnicity, age of diagnosis, and gender. In all, 21 of 34 CD-associated SNPs had similar allele frequencies in UC (n = 1230) and CD (n = 1144). Three of six UC-associated SNPs had significantly different frequencies in CD (n = 1144). Most of the divergence in allele frequency among CD and UC was noted in NOD2/autophagy pathway SNPs, while most SNPs with similar frequencies were in IL-22/23 Th17, adaptive immunity, and barrier pathways. Colon-only CD (n = 228) was compared with healthy controls: three of six UC SNPs (in MST1, HLA-DRA, and IL-23R) and 11 of 34 CD SNPs: in IRGM, NOD2 (rs2066845), CCNY, MST1, IL23R, PTPN22, C11orf30, ZNF365, PTPN2, PSMG1, and rs1456893 were significantly associated. In all, 29 of 34 CD SNPs had similar allele frequencies in colonic CD compared with ileal CD (n = 366). All UC SNPs had similar frequencies in UC and colonic CD. Our results suggest that CD and UC share common genetic associations related to impaired adaptive immunity and diverge in pathways of foreign antigen processing. Colon-only CD overlaps extensively with UC and considerably with ileal CD.
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溃疡性结肠炎中克罗恩病风险的研究进一步定义了它们的分子关系。
影响因子：
29.4
作者：
Anderson CA;Massey DC;Barrett JC;Prescott NJ;Tremelling M;Fisher SA;Gwilliam R;Jacob J;Nimmo ER;Drummond H;Lees CW;Onnie CM;Hanson C;Blaszczyk K;Ravindrarajah R;Hunt S;Varma D;Hammond N;Lewis G;Attlesey H;Watkins N;Ouwehand W;Strachan D;McArdle W;Lewis CM;Wellcome Trust Case Control Consortium;Lobo A;Sanderson J;Jewell DP;Deloukas P;Mansfield JC;Mathew CG;Satsangi J;Parkes M
通讯作者：
Parkes M
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：
Kugathasan, Subra;Baldassano, Robert N.;Bradfield, Jonathan P.;Sleiman, Patrick M. A.;Imielinski, Marcin;Guthery, Stephen L.;Cucchiara, Salvatore;Kim, Cecilia E.;Frackelton, Edward C.;Annaiah, Kiran;Glessner, Joseph T.;Santa, Erin;Willson, Tara;Eckert, Andrew W.;Bonkowski, Erin;Shaner, Julie L.;Smith, Ryan M.;Otieno, F. George;Peterson, Nicholas;Abrams, Debra J.;Chiavacci, Rosetta M.;Grundmeier, Robert;Mamula, Petar;Tomer, Gitit;Piccoli, David A.;Monos, Dimitri S.;Annese, Vito;Denson, Lee A.;Grant, Struan F. A.;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
30.8
作者：
Imielinski, Marcin;Baldassano, Robert N.;Griffiths, Anne;Russell, Richard K.;Annese, Vito;Dubinsky, Marla;Kugathasan, Subra;Bradfield, Jonathan P.;Walters, Thomas D.;Sleiman, Patrick;Kim, Cecilia E.;Muise, Aleixo;Wang, Kai;Glessner, Joseph T.;Saeed, Shehzad;Zhang, Haitao;Frackelton, Edward C.;Hou, Cuiping;Flory, James H.;Otieno, George;Chiavacci, Rosetta M.;Grundmeier, Robert;Castro, Massimo;Latiano, Anna;Dallapiccola, Bruno;Stempak, Joanne;Abrams, Debra J.;Taylor, Kent;McGovern, Dermot;Heyman, Melvin B.;Ferry, George D.;Kirschner, Barbara;Lee, Jessica;Essers, Jonah;Grand, Richard;Stephens, Michael;Levine, Arie;Piccoli, David;Van Limbergen, Johan;Cucchiara, Salvatore;Monos, Dimitri S.;Guthery, Stephen L.;Denson, Lee;Wilson, David C.;Grant, Struan F. A.;Daly, Mark;Silverberg, Mark S.;Satsangi, Jack;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
8
作者：
Goyette, P.;Lefebvre, C.;Rioux, J. D.
通讯作者：
Rioux, J. D.