Abstract for presentation at 11th International Congress of Human Genetics

Susceptibility genes in New Zealand Crohn’s disease patients

  • Ms Jiwon Hong, Department of Molecular Medicine & Pathology, University of Auckland, Auckland, New Zealand
  • Dr Euphemia Leung, Department of Molecular Medicine & Pathology, University of Auckland, Auckland, New Zealand
  • Dr Tony Merriman, Department of Biochemistry, University of Otago, Dunedin, New Zealand
  • A/Prof Alan Fraser, Department of Medicine, University of Auckland, Auckland, New Zealand
  • A/Prof Geoffrey Krissansen, Department of Molecular Medicine & Pathology, University of Auckland, Auckland, New Zealand

    • Crohn’s disease (CD) is a chronic inflammatory gut disease affecting ~1 in 1000 people in western countries. It usually starts in the third decade of life and may cause ongoing problems including abdominal pain, cramping, diarrhea, bleeding, fever, and weight loss. The prevailing theory is that the body’s immune system in genetically susceptible individuals responds inappropriately to intestinal bacteria. Recently, a gene called CARD15 (NOD2) was found to be mutated in up to 50% of CD patients. The encoded NOD2 protein is a pattern recognition receptor (PRR), which helps the innate immune system recognize and respond to bacteria. We have found that the allelic frequencies of major CARD15 variants (3020insC, G908R, R702W) are low in CD patients in New Zealand. Nevertheless, the 3020insC was found to be associated with CD (P < 0.0001) and increases the risk of terminal ileum disease and need for surgery. Aim: CD is thought to be a multigene disease where the risk of developing the disease depends on the number and type of susceptibility genes you inherit. Therefore, we aimed to identify additional gene polymorphisms that may increase the risk of CD in New Zealand. Methods: The frequency of gene polymorphisms was examined in 182 CD patients and 188 ethnically-matched controls by PCR-RFLP. Results: We screened for polymorphisms in several candidate genes including PRRs (CD14[-159C/T] and Toll-like receptors TLR2[R753Q], TLR4[D299G, T399I], TLR9[-1237T/C]), cytokines (TNFa[-308G/A, -863C/A], IL4[-34C/T], IL10[-592C/A, -1082G/A, G15A], and IL16[-295T/C]), as well as NFKBIA[3’UTR 2758G/A], ICAM1[K469E], CSF1R[2033A/T], OCTN1[1672C/T] and OCTN2[-207G/C], and PPARγ[C681G, G12350898A, P12A]. The OCTN1/2 TC haplotype is associated (P = 0.029) with CD in New Zealand, and with an ileocolonic location (P = 0.0007). There was no evidence that other candidate polymorphisms are associated with CD. Conclusion: Only damaged CARD15 and OCTN were the significant risk factors for New Zealand CD patients.

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