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©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Aug 7, 2008; 14(29): 4643-4651
Published online Aug 7, 2008. doi: 10.3748/wjg.14.4643
Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy
Anna Latiano, Orazio Palmieri, Maria Rosa Valvano, Renata D’Incà, Salvatore Cucchiara, Gabriele Riegler, Anna Maria Staiano, Sandro Ardizzone, Salvatore Accomando, Gian Luigi de Angelis, Giuseppe Corritore, Fabrizio Bossa, Vito Annese
Anna Latiano, Orazio Palmieri, Maria Rosa Valvano, Giuseppe Corritore, Fabrizio Bossa, Vito Annese, U.U. O.O. di Gastroenterologia ed Endoscopia, Ospedale IRCCS-CSS, San Giovanni Rotondo (Fg) 71013, Italy
Renata D’Incà, Cattedra di Gastroenterologia, Università di Padova, Padova 35122, Italy
Salvatore Cucchiara, Clinica Pediatrica Università“La Sapienza”, Roma 00185, Italy
Gabriele Riegler, Cattedra di Gastroenterologia, Università di Napoli, Napoli 80131, Italy
Anna Maria Staiano, Clinica Pediatrica Università di Napoli, Napoli 80131, Italy
Sandro Ardizzone, Unità di Gastroenterologia, Ospedale “Sacco”, Milano 20157, Italy
Salvatore Accomando, Clinica Pediatrica Università di Palermo, Palermo 90128, Italy
Gian Luigi de Angelis, Clinica Pediatrica Università di Parma, Parma 43100, Italy
Author contributions: Latiano A and Annese V contributed equally to this work, designed and overviewed the study, and wrote the paper; Palmieri O overviewed and designed the genotyping, Valvano MR analyzed the data, D'Incà R, Cucchiara S, Riegler G, Staiano AM, Ardizzone S, Accomando S, de Angelis GL, Bossa F and Annese V provided DNA samples and clinical information; Corritore G performed the genotyping.
Correspondence to: Dr. Vito Annese, Struttura Complessa di Endoscopia Digestiva, Ospedale “Casa Sollievo della Sofferenza” - I.R.C.C.S., Viale Cappuccini, 1, San Giovanni Rotondo 71013, Italy.
v.annese@operapadrepio.it
Telephone: +39-882-410235
Fax: +39-882-410784
Received: April 29, 2008
Revised: July 14, 2008
Accepted: July 21, 2008
Published online: August 7, 2008
AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes.
METHODS: Total of 763 patients with Crohn’s disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed < 19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped.
RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced significantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15, and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease.
CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.
