Digestive and Liver Disease 36 (2004) 121–124 Alimentary Tract Frequency of NOD 2 /CARD 15 variants in both sporadic and familial cases of Crohn’s disease across Italy An Italian Group for Inflammatory Bowel Disease study V. Annese a,* , O. Palmieri a,b , A. Latiano a , S. Ardizzone c , F. Castiglione d , M. Cottone e , R. D’Incà f , P. Gionchetti g , C. Papi h , G. Riegler i , M. Vecchi j , A. Andriulli a a Department of General and Specialist Medicine, Unit of Gastroenterology, CSS-IRCCS Hospital, Viale Cappuccini, 1, 71013 San Giovanni Rotondo, Italy b Div. Genetics, Thomas Jefferson University, Philadelphia, PA, USA c Unit of Gastroenterology, “L. Sacco” University Hospital Milan, Milan, Italy d Unit of Gastroenterology, 1 University of Naples, Naples, Italy e Institute of Internal Medicine & Gastroenterology, “Cervello” Hospital, Palermo, Italy f Unit of Gastroenterology, University of Padua, Padua, Italy g Institute of Internal Medicine & Gastroenterolgy, “S. Orsola” University Hospital, Bologna, Italy h Unit of Gastroenterology, “S. Filippo Neri” Hospital, Rome, Italy i Unit of Gastroenterology, II University of Naples, Naples, Italy j Unit of Gastroenterology, “Maggiore” Hospital, IRCCS, Milan, Italy Received 30 July 2003; accepted 22 October 2003 Abstract Background. Three variants of the NOD 2 /CARD 15 gene are strongly associated with susceptibility to Crohn’s disease; however, striking racial and geographic differences of their frequency have been described. Aims. We have compared the allele frequencies of familial cases of Crohn’s disease recruited in a multicentre study across Italy, in order to disclose possible geographic heterogeneity. Moreover, we also compared the allele frequencies in sporadic cases of Crohn’s disease and healthy controls from Southern Italy with those reported in other two populations from Central and Northern Italy. Subjects and Methods. A total of 731 subjects were genotyped for the polymorphism of three main variants (R702W, G908R and 1007 fs): 152 patients were familial cases of Crohn’s disease, 183 were healthy first-degree relatives, 180 were sporadic cases of Crohn’s disease, and 216 were unrelated healthy subjects. Results. The frequency of the frameshift mutation (1007 fs) was significantly higher in both familial and sporadic cases of Crohn’s disease (P = 0.000001), and healthy first-degree relatives (P = 0.0001) compared to controls. At least one risk allele was found in 44% of familial Crohn’s disease patients, compared to 7% of healthy controls (OR = 4; CI = 2–6.5). Two risk alleles were found in 14% of familial Crohn’s disease, compared to less than 1% of controls (OR = 26: CI = 4–129). Conclusions. Our data confirm the strong correlation between the 1007 fs variant and Crohn’s disease, in both familial and sporadic cases. Moreover, no significant difference of allele frequencies was detected in familial cases, sporadic cases and healthy controls among different geographic areas of Italy. © 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: CARD 15 ; Crohn’s disease; Genetics; Inflammatory bowel disease; NOD 2 * Corresponding author. Tel.: +39-0882-410235-335; fax: +39-0882-411879/411705. E-mail address: vito.annese@tin.it (V. Annese). 1. Introduction Three major polymorphisms of the NOD 2 /CARD 15 gene, a frameshift mutation (1007 fs) encoding for a truncated pro- tein and two missense mutations (R702W and G908R), have been found associated with susceptibility to Crohn’s disease 1590-8658/$30 © 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2003.10.010