Analysis of the influence of two CD24 genetic variants in Crohn’s disease and ulcerative colitis Lina-Marcela Diaz-Gallo a, *, Luz MarÎa Medrano b , MarÎa GÔmez-GarcÎa c , Carlos CardeÒa d , Luis Rodrigo e , Juan Luis Mendoza f , Carlos Taxonera f , Antonio Nieto g , Guillermo Alcain h , Ignacio Cueto h , Miguel A. LÔpez-Nevot i , Elena Urcelay b , Javier Martin a a Instituto de Parasitologìa y Biomedicina “Lòpez-Neyra,” Consejo Superior de Investigaciones Cientìficas (CSIC), Granada, Spain b Department of Clinical Immunology, Hospital Clìnico S. Carlos, Madrid, Spain c Department of Gastroenterology, Hospital Virgen de las Nieves, Granada, Spain d Department of Gastroenterology, Hospital Clìnico San Cecilio, Granada, Spain e Department of Gastroenterology, Hospital Central de, Asturias, Oviedo, Spain f Department of Gastroenterology, Hospital Universitario S, Carlos, Madrid, Spain g Department of Immunology, Hospital Puerta del Mar, Càdiz, Spain h Department of Gastroenterology, Hospital Virgen de la Victoria, Màlaga, Spain i Department of Immunology, Hospital Virgen de las Nieves, Granada, Spain ARTICLE INFO Article history: Received 19 January 2011 Accepted 25 May 2011 Available online 17 June 2011 Keywords: CD24 gene Crohn’s disease Ulcerative colitis ABSTRACT The aim of this study was to evaluate the possible implication of CD24 gene in the genetic predisposition to inflammatory bowel disease (IBD). Our study population consisted of 1321 female Spanish individuals (369 Crohn’s disease [CD] patients, 323 ulcerative colitis [UC] patients, and 629 healthy matched controls). Two putative functional polymorphisms, a C to T coding polymorphism (rs8734) and a TG deletion in the 3= untranslated region (rs3838646), were used as CD24 genetic markers and genotyped using a Taqman 5= allelic discrimination assay. The “del” allele of the dinucleotide deletion was associated with an increased risk of CD (odds ratio = 1.61, 95% confidence interval = 1.17–2.21, p FDR = 6.4E-03) but not with UC. Moreover, this allele was significant associated with the age of CD diagnosis between 17 and 40 years, the ileocolonic location, and the inflammatory behavior of CD. We observed no significant differences between the allelic or genotypic frequencies of the A57V polymorphism in our studied IBD cohort. Our results suggest that the rs3838646 CD24 polymorphism is part of the genetic background of CD.  2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Crohn’s disease (CD) and ulcerative colitis (UC) are the main clinical phenotypes of inflammatory bowel disease (IBD). Both are relapsing and chronic inflammatory disorders that result from the complex interaction of genetic, immune, and environmental fac- tors. There is an increasingly long list of genetic factors associated with IBD. However, it is estimated that the current number of loci associated with IBD represents only a small fraction of the genetic risk [1–3]. Thus, additional genetic contributions clearly remain to be discovered. The CD24 gene encodes a small (ranging between 20 and 70 amino acids), heavily glycosylated protein that is attached to the cell membrane by a glyco-phosphotidyl-inistol [GPI] anchor and is expressed in a broad range of cell types [4]. CD24, referred to as a B-cell differentiation marker at first, plays crucial roles in lympho- cyte maturation [5,6,7], neuronal development [8], and tissue re- newal homeostasis under physiologic conditions [9]. This molecule has been proposed as a genetic checkpoint in T-cell homoeostasis and pathogenesis of autoimmune diseases [10]. Moreover, the CD24 gene has been recently added to the list of putative intestinal stem cell markers [8,11] and it has been demonstrated that is up-regulated in regenerative mucosa in both UC and CD [12]. By contrast, two functional genetic polymorphisms, a C to T coding polymorphism (rs8734) [13] and a TG deletion in the 3= untrans- lated region (rs3838646) [14], have been associated as susceptibil- ity factors for multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and giant cell arthritis (GCA) [13–19]. The aim of this study was to investigate the potential implication of the rs8734 and rs3838646 CD24 gene functional variants in the genetic susceptibility to IBD. 2. Subjects and methods Our study included 692 IBD female Spanish patients (371 with CD and 323 with UC) meeting the standard clinical, endoscopic, * Corresponding author. E-mail address: lina.diaz@ipb.csic.es (L.-M. Diaz-Gallo). E.U. and J.M. contribute equally to this work. Human Immunology 72 (2011) 969-972 Contents lists available at SciVerse ScienceDirect 0198-8859/11/$32.00 - see front matter  2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.humimm.2011.05.028