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Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy

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World Journal of Gastroenterology 2008年第29期14卷 4643-4651页

作者： 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 U.U. O.O. di Gastroenterologia ed Endoscopia Ospedale IRCCS-CSSSan Giovanni Rotondo (Fg) 71013 Italy Cattedra di Gastroenterologia Università di PadovaPadova 35122 Italy Clinica Pediatrica Università "La Sapienza" Roma 00185 Italy Cattedra di Gastroenterologia Università di NapoliNapoli 80131 Italy Clinica Pediatrica Università di Napoli Napoli 80131 Italy Unità di Gastroenterologia Ospedale "Sacco" Milano 20157 Italy Clinica Pediatrica Università di Palermo Palermo 90128 Italy Clinica Pediatrica Università di Parma Parma 43100 Italy

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 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 16L1 with CD, in both adult- and pediatric-onset subsets in our study population.

关键词： Inflammatory bowel disease Crohn'sdisease Ulcerative colitis Genetic predisposition autophagy-related 16-like 1 Interleukin 23 receptor Genome-wide association study Pediatric inflammatorybowel disease

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Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients

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World Journal of Gastroenterology 2010年第2期16卷 176-183页

作者： Veronika Csngei Luca Járomi EnikSáfrány Csilla Sipeky Lili Magyari Bernadett Faragó Judit Bene Noémi Polgár Lilla Lakner Patrícia Sarlós Márta Varga Béla Melegh Department of Medical Genetics University of Pécs Department of Medicine and Gastroenterology Markusovszky Hospital 3rd Department of Internal Medicine University of Pécs 3rd Department of Medicine and Gastroenterology Réthy Pál Hospital

AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were *** and specific genotype combinations of a total of eight variants were *** variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease *** also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk *** almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one *** highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.

关键词： Gene interaction Interleukin-23 receptor autophagy-related 16-like 1 IBD5 Caspase recruitment domain-containing protein 15 Crohn’s disease Inflammatory bowel disease

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