NOD2/CARD15 gene polymorphisms and Crohn’s disease in the Chinese population R. W. L. LEONG*, A. ARMUZZI  , T. AHMAD  , M. L. WONG*, P. TSE*, D. P. JEWELL  & J. J. Y. SUNG* *Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China;  Department of Gastroenterology, University of Oxford, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK Accepted for publication 6 April 2003 SUMMARY Background: Crohn’s disease affects people world-wide, but the incidence in Asia is lower than in Western countries. This difference may be due to genetic and/or environmental factors. Three single nucleotide poly- morphisms (SNPs) of the NOD2/CARD15 gene have been identified to be independently associated with the development of Crohn’s disease in Caucasians. Whether these SNPs are involved in the pathogenesis of Crohn’s disease in the Chinese population is unknown. Aim: To determine if NOD2/CARD15 gene polymor- phisms are found in Chinese patients with Crohn’s disease. Methods: Sixty-five consecutive Chinese Crohn’s disease patients had genotyping performed using sequence- specific PCR directed against the wild-type and the Arg702Trp, Gly908Arg and 3020insC variants of the NOD2/CARD15 gene. Controls consisted of 63 patients with ulcerative colitis and 70 patients with dyspepsia. Results: None of the patients with Crohn’s disease had heterozygous or homozygous SNP variants. Similarly none of the ulcerative colitis or dyspeptic controls had these SNPs. Conclusion: The three previously described SNPs associ- ated with the development of Crohn’s disease in Caucasians are not found in Chinese patients with Crohn’s disease. INTRODUCTION It is widely accepted that genetic factors play an important role in the pathogenesis of Crohn’s disease. 1 Linkage analysis studies have previously identified the IBD1 locus at the pericentromeric region of chromo- some 16 as a marker of increased Crohn’s disease susceptibility. 2–6 More recently, NOD2, a member of the NOD1/APAF1 gene family, was identified and mapped to chromosome 16q12. 7 Independent groups have now reported that mutations in the NOD2 gene are associ- ated with increased susceptibility to Crohn’s disease. 8–10 The NOD2 gene was subsequently renamed CARD15, emphasizing the two caspase recruitment domains located at the N-terminus of the gene. The NOD2/ CARD15 gene product is expressed in monocytes, and is involved in the binding of bacteria lipopolysaccharides and peptidoglycans, activation of nuclear transcription factor kappa-B (NF-jB) and in inflammatory response. 8, 11 In addition, there is structural homology with both the apoptosis regulators Apaf-1/Ced-4 and a class of plant disease-resistant (R) gene products, suggesting a role for this gene in host resistance against microbiological products. 7 Two mis-sense mutations (Arg702Trp and Gly908Arg) and one frame-shift mutation (3020insC) of the NOD2/CARD15 gene are independently associated with the development of Crohn’s disease. These mutations affect the structure of the leucine-rich repeat (LRR) domain of the gene product or the adjacent region, which may be the site of binding of microbial pathogens. 9 In particular, these NOD2/CARD15 single nucleotide polymorphisms Correspondence to: Dr R. Leong, University of New South Wales, Depart- ment of Gastroenterology, Bankstown Hospital, Eldridge Road, Bankstown 2200, Sydney, NSW, Australia. E-mail: rupertleong@hotmail.com Aliment Pharmacol Ther 2003; 17: 1465–1470. doi: 10.1046/j.0269-2813.2003.01607.x Ó 2003 Blackwell Publishing Ltd 1465