Differential Association of Two PTPN22 Coding Variants with Crohn's Disease and Ulcerative Colitis

被引:67
|
作者
Diaz-Gallo, Lina-Marcela [1 ]
Espino-Paisan, Laura [2 ]
Fransen, Karin [3 ,4 ]
Gomez-Garcia, Maria [6 ]
van Sommeren, Suzanne [3 ]
Cardena, Carlos [5 ]
Rodrigo, Luis [7 ]
Mendoza, Juan Luis [8 ]
Taxonera, Carlos [8 ]
Nieto, Antonio [9 ]
Alcain, Guillermo [10 ]
Cueto, Ignacio [10 ]
Lopez-Nevot, Miguel A. [11 ]
Bottini, Nunzio [12 ]
Barclay, Murray L. [13 ]
Crusius, J. Bart [14 ]
van Bodegraven, Adriaan A. [15 ]
Wijmenga, Cisca [4 ]
Ponsioen, Cyriel Y. [16 ]
Gearry, Richard B. [13 ]
Roberts, Rebecca L. [17 ]
Weersma, Rinse K. [3 ]
Urcelay, Elena [2 ]
Merriman, Tony R. [17 ]
Alizadeh, Behrooz Z. [18 ]
Martin, Javier [1 ]
机构
[1] CSIC, Inst Parasitol & Biomed Lopez Neyra, Armilla 18100, Granada, Spain
[2] Hosp Clin S Carlos, Dept Clin Immunol, Madrid, Spain
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, NL-9713 AV Groningen, Netherlands
[4] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands
[5] Hosp Clin San Cecilio, Dept Gastroenterol, Granada, Spain
[6] Hosp Virgen Nieves, Dept Gastroenterol, Granada, Spain
[7] Univ Oviedo, Hosp Cent Asturias, Dept Gastroenterol, E-33080 Oviedo, Spain
[8] Hosp Univ S Carlos, Dept Gastroenterol, Madrid, Spain
[9] Hosp Puerta Mar, Dept Immunol, Cadiz, Spain
[10] Hosp Virgen Victoria, Dept Gastroenterol, Malaga, Spain
[11] Hosp Virgen Nieves, Dept Immunol, Granada, Spain
[12] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA USA
[13] Univ Otago, Dept Med, Christchurch, New Zealand
[14] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Immunogenet Lab, Amsterdam, Netherlands
[15] Vrije Univ Amsterdam Med Ctr, Dept Gastroenterol, Amsterdam, Netherlands
[16] Acad Med Ctr Amsterdam, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands
[17] Univ Otago, Dept Biochem, Dunedin, New Zealand
[18] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, NL-9713 AV Groningen, Netherlands
关键词
protein tyrosine phosphatase; nonreceptor type 22 (PTPN22) gene; inflammatory bowel disease (IBD); ulcerative colitis (UC); Crohn's disease (CD); GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; LYMPHOID TYROSINE PHOSPHATASE; 7 COMMON DISEASES; AUTOIMMUNE-DISEASES; SUSCEPTIBILITY LOCI; RISK LOCI; POPULATION; GENE; MULTIPLE;
D O I
10.1002/ibd.21630
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn's disease (CD), and to reevaluate the association of the R620W PTPN22 polymorphism with both diseases. Methods: A total of 1677 UC patients, 1903 CD patients, and 3111 healthy controls from an initial case-control set of Spanish Caucasian ancestry and two independent sample sets of European ancestry (Dutch and New Zealand) were included in the study. Genotyping was performed using TaqMan SNP assays for the R263Q (rs33996649) and R620W (rs2476601) PTPN22 polymorphisms. Meta-analysis was performed on 6977 CD patients, 5695 UC patients, and 9254 controls to test the overall effect of the minor allele of R620W and R263Q polymorphisms. Results: The PTPN22 263Q loss-of-function variant showed initial evidence of association with UC in the Spanish cohort (P =0.026, odds ratio [OR] = 0.61, 95% confidence interval [CI]: 0.39-0.95), which was confirmed in the meta-analysis (P = 0.013 pooled, OR 0.69, 95% CI: 0.51-0.93). In contrast, the 263Q allele showed no association with CD (P = 0.22 pooled, OR = 1.16, 95% CI: 0.91-1.47). We found in the pooled analysis that the PTPN22 620W gain-of-function variant was associated with reduced risk of CD (P = 7.4E-06 pooled OR 0.81, 95% CI: 0.75-0.89) but not of UC (P = 0.88 pooled, OR = 0.98, 95% CI: 0.85-1.15). Conclusions: Our data suggest that two autoimmunity-associated polymorphisms of the PTPN22 gene are differentially associated with CD and UC. The R263Q polymorphism only associated with UC, whereas the R620W was significantly associated with only CD. (Inflamm Bowel Dis 2011;17:2287-2294)
引用
收藏
页码:2287 / 2294
页数:8
相关论文
共 50 条
  • [41] Differential expression in colitis-associated cancer compared with Crohn's disease and ulcerative colitis
    Sehn, M.
    Elezkurtaj, S.
    da Silva, D. Cardoso
    Siegmund, B.
    Kreis, M.
    Holmer, C.
    Hummel, M.
    Groene, J.
    Schumann, M.
    JOURNAL OF CROHNS & COLITIS, 2018, 12 : S147 - S148
  • [42] Differential expression in colitis-associated cancer compared to Crohn's disease and ulcerative colitis
    Manna, S.
    Sehn, M.
    da Silva, D. Cardoso
    Elezkurtaj, S.
    Cineus, R.
    Hegazy, A.
    Siegmund, B.
    Weixler, B.
    Hummel, M. L.
    Grone, J.
    Schumann, M.
    JOURNAL OF CROHNS & COLITIS, 2021, 15 : S135 - S135
  • [43] Differential expression of HLA-G in Crohn's disease and ulcerative colitis
    Wilcox, R
    Yilmaz, B
    Gong, C
    Tretiakova, M
    Huo, D
    Cho, J
    Noffsinger, A
    Hart, J
    LABORATORY INVESTIGATION, 2006, 86 : 124A - 124A
  • [44] Differential expression of HLA-G in Crohn's disease and ulcerative colitis
    Wilcox, R
    Yilmaz, B
    Gong, C
    Tretiakova, M
    Huo, D
    Cho, J
    Noffsinger, A
    Hart, J
    MODERN PATHOLOGY, 2006, 19 : 124A - 124A
  • [45] Endoscopic ultrasonography in the differential diagnosis of Ulcerative colitis and Crohn's disease.
    Belousova, E.
    Budzinskay, A.
    Belousova, E.
    Lomakina, E.
    Levitskaya, A.
    JOURNAL OF CROHNS & COLITIS, 2023, 17 : 501 - 501
  • [46] Isolation of peptides useful for differential diagnosis of Crohn's disease and ulcerative colitis
    Saito, H
    Fukuda, Y
    Katsuragi, K
    Tanaka, M
    Satomi, M
    Shimoyama, T
    Saito, T
    Tachikawa, T
    GUT, 2003, 52 (04) : 535 - 540
  • [47] Differential Impact of Smoking on Methylome and Transcriptome in Crohn's Disease and Ulcerative Colitis
    Ang, Qi Yan
    Plichta, Damian
    Kim, Sean
    Kim, Iris Hyun-A
    Gregory, Sadie
    Xia, Yan
    Lau, Helena
    Xavier, Ramnik
    Ananthakrishnan, Ashwin N.
    INFLAMMATORY BOWEL DISEASES, 2024, 30 (06) : 981 - 991
  • [48] Differential Intestinal Mucosa Transcriptomic Biomarkers for Crohn's Disease and Ulcerative Colitis
    Dobre, Maria
    Milanesi, Elena
    Manuc, Teodora Ecaterina
    Arsene, Dorel Eugen
    Tieranu, Cristian George
    Maj, Carlo
    Becheanu, Gabriel
    Manuc, Mircea
    JOURNAL OF IMMUNOLOGY RESEARCH, 2018, 2018
  • [49] ANCA/ASCA differential diagnosis between ulcerative colitis and Crohn's disease?
    Joossens, S
    Vandewalle, P
    Vermeire, S
    Sendid, B
    Poulain, D
    Rutgeerts, P
    Colombel, JF
    VI INTERNATIONAL SYMPOSIUM ON INFLAMMATORY BOWEL DISEASES, 2002, 123 : 39 - 46
  • [50] Pathogenesis of Crohn's disease and ulcerative colitis
    Autschbach, F
    Otto, HF
    CHIRURGISCHE GASTROENTEROLOGIE, 1998, 14 (02): : 98 - 103