Abstract
Purpose
Aseptic abscesses syndrome (AA) is an inflammatory disease in which non-infectious deep abscesses develop; these respond quickly to corticosteroids. AA is associated with Crohn disease (CD) in 57% of cases and with neutrophilic dermatosis (ND) in 20%. Pyoderma gangrenosum is usually a sporadic ND. A hereditary autosomal dominant syndromic kind of pyoderma gangrenosum, the PAPA syndrome, is linked to mutations in the CD2BP1/PSTPIP1 gene. We systematically screened this gene in French AA patients.
Results
One microsatellite (CCTG)n with 3 alleles was identified in the promoter. The longest form (CCTG)7 was significantly more frequent in AA patients than in French controls (P = 0.0154). We also found an association of the (CCTG)7 allele with CD in French patients (P = 0.0351). This association was not found in a sample of Indian patients.
Conclusions
The CCTG repeat in the PSTPIP1 promoter may play a role in the pathogenesis of AA and of CD. Further investigations are required to demonstrate the possible modulation of gene expression by the (CCTG)n motif.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
André MF, Piette JC, Kemeny JL, et al. Aseptic abscesses: a study of 30 patients with or without inflammatory bowel disease and review of the literature. Medicine. 2007;86:145–161.
André MF, Aumaître O, Piette JC, et al. Analysis of the NOD2/CARD15 gene in patients affected with the aseptic abscesses syndrome with or without inflammatory bowel disease. Dig Dis Sci. 2008;53:490–499.
Wallach D. Neutrophilic dermatoses: an overview. Clin Dermatol. 2000;18:229–231.
Lindor NM, Arsenault TM, Solomon H, Seidman CE, McEvoy MT. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome. Mayo Clin Proc. 1997;72:611–615.
Yeon HB, Lindor NM, Seidman JG, Seidman CE. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. Am J Hum Genet. 2000;66:1443–1448.
Wise CA, Gillum JD, Seidman CE, et al. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002;11:961–969.
Li J, Nishizawa K, An W, et al. A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion. EMBO J. 1998;17:7320–7336.
Yang H, Reinherz EL. CD2BP1 modulates CD2-dependent T cell activation via linkage to protein tyrosine phosphatase (PTP)-PEST. J Immunol. 2006;176:5898–5907.
Badour K, Zhang J, Shi F, et al. The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse. Immunity. 2003;18:141–154.
The French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet. 1997;17:25–31.
The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell. 1997;90:797–807.
Shoham NG, Centola M, Mansfield E, et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci. 2003;100:13501–13506.
Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6.
Holzenberger M, Lenzner C, Leneuve P, et al. Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene. Nucleic Acids Res. 2000;28:e92.
Newman B, Cescon D, Domenchini A, Siminovitch KA. CD2BP1 and CARD15 mutations are not associated with pyoderma gangrenosum in patients with inflammatory bowel disease. J Invest Dermatol. 2004;122:1054–1056.
Raymond M, Rousset F. GENEPOP (version 1.2). Population genetics software for exact tests and ecumenicism. J Heredity. 1995;86:248–249.
Ah-Weng A, Langtry JA, Velangi S, Evans CD, Douglas WS. Pyoderma gangrenosum associated with hidradenitis suppurativa. Clin Exp Dermatol. 2005;30:669–671.
Iglesias AR, Kindlund E, Tammi M, Wadelius C. Some microsatellites may act as novel polymorphic cis-regulatory elements through transcription factor binding. Gene. 2004;341:149–165.
Brant SR, Shugart YY. Inflammatory bowel disease gene hunting by linkage analysis: rationale, methodology, and present status of the field. Inflamm Bowel Dis. 2004;10:300–311.
Kojima Y, Kinouchi Y, Takahashi S, Negoro K, Hiwatashi N, Shimosegawa T. Inflammatory bowel disease is associated with a novel promoter polymorphism of natural resistance-associated macrophage protein 1 (NRAMP1) gene. Tissue Antigens. 2001;58:379–384.
Negoro K, Kinouchi Y, Hiwatashi N, et al. Crohn’s disease is associated with novel polymorphisms in the 5′-flanking region of the tumor necrosis factor gene. Gastroenterology. 1999;117:1062–1068.
Acknowledgments
We are particularly grateful to the patients with AA and the physicians who took part in this study, to Vanessa Pereira for technical assistance, to Lemlih Ouchchane and Mr. Chenaf who supervised statistical data, to Jeffrey Watts and Sam Smith for keep in preparing the English manuscript, and to Srikanth Santhanam and Jean-Frédéric Colombel. This work was supported by Grant PHRC 2004/CHU Clermont-Ferrand. Marc André is a recipient of a Contrat d’Interface Inserm-CHU Clermont-Ferrand.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
André, M.F.J., Aumaître, O., Grateau, G. et al. Longest Form of CCTG Microsatellite Repeat in the Promoter of the CD2BP1/PSTPIP1 Gene Is Associated with Aseptic Abscesses and with Crohn Disease in French Patients. Dig Dis Sci 55, 1681–1688 (2010). https://doi.org/10.1007/s10620-009-0929-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-009-0929-7