Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jan 14, 2010; 16(2): 176-183
Published online Jan 14, 2010. doi: 10.3748/wjg.v16.i2.176
Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients
Veronika Csöngei, Luca Járomi, Enikő Sáfrány, Csilla Sipeky, Lili Magyari, Bernadett Faragó, Judit Bene, Noémi Polgár, Lilla Lakner, Patrícia Sarlós, Márta Varga, Béla Melegh
Veronika Csöngei, Luca Járomi, Enikő Sáfrány, Csilla Sipeky, Lili Magyari, Bernadett Faragó, Judit Bene, Noémi Polgár, Béla Melegh, Department of Medical Genetics, University of Pécs, Pécs 7624, Hungary
Lilla Lakner, Department of Medicine and Gastroenterology, Markusovszky Hospital, Szombathely 9700, Hungary
Patrícia Sarlós, 3rd Department of Internal Medicine, University of Pécs, Pécs 7624, Hungary
Márta Varga, 3rd Department of Medicine and Gastroenterology, Réthy Pál Hospital, Békéscsaba 5600, Hungary
Author contributions: Csöngei V and Járomi L performed the genotyping and analyzed the data; Sáfrány E, Sipeky C, Magyari L, Faragó B and Bene J designed and performed the genotyping and were also involved in editing the manuscript; Polgár N overviewed the genotyping and revised the paper; Lakner L, Sarlós P and Varga M contributed human subjects and DNA samples; Melegh B designed and overviewed the study; Csöngei V wrote the manuscript.
Supported by Grant of Hungarian Scientific Research Foundation, No. OTKA T 73430
Correspondence to: Béla Melegh, MD, PhD, DSc, Professor, Chairman, Department of Medical Genetics, University of Pécs, Pécs 7624, Hungary. bela.melegh@aok.pte.hu
Telephone: +36-72-536427 Fax: +36-72-536032
Received: July 24, 2009
Revised: September 22, 2009
Accepted: September 29, 2009
Published online: January 14, 2010
Abstract

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 genotyped. Interactions and specific genotype combinations of a total of eight variants were tested. The variants of IBD5 locus (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; P < 0.001, OR = 2.97, 95% CI: 1.65-5.33 for rs2201841 CC). Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD) loci indicated that IL23R, ATG16L1, CARD15 and IBD5 (IGR2198a_1) contribute independently to disease risk. We also analysed the specific combinations by pair of individual ATG16L1, IL23R rs1004819, rs2201841, IGR2198a_1, IGR2096a_1 and CARD15 genotypes for disease risk influence. In 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 polymorphism. The 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.

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