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

Veronika Csöngei, Luca Járomi, Eniko Sáfrány, Csilla Sipeky, Lili Magyari, Bernadett Faragó, Judit Bene, Noémi Polgár, Lilla Lakner, Patrícia Sarlós, Márta Varga, Béla Melegh

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)176-183
Number of pages8
JournalWorld journal of gastroenterology
Volume16
Issue number2
DOIs
Publication statusPublished - Jan 14 2010

Keywords

  • Autophagy-related 16-like 1
  • Caspase recruitment domain-containing protein 15
  • Crohn's disease
  • Gene interaction
  • IBD5
  • Inflammatory bowel disease
  • Interleukin-23 receptor

ASJC Scopus subject areas

  • Gastroenterology

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