Prevalence of CARD15/NOD2 Mutations in Caucasian Healthy People

Hugot, Jean-Pierre; Zaccaria, Isabelle; Cavanaugh, Juleen; Yang, Huiying; Vermeire, Séverine; Lappalainen, Maarit; Schreiber, Stefan; Annese, Vito; Jewell, Derek P.; Fowler, Elizabeth V.; Brant, Steven R.; Silverberg, Mark S.; Cho, Judy; Rioux, John D.; Satsangi, Jack; Parkes, Miles
June 2007
American Journal of Gastroenterology;Jun2007, Vol. 102 Issue 6, p1259
Academic Journal
BACKGROUND: Crohn's disease (CD) has been associated with CARD15/NOD2 mutations in Caucasians. The R702W, G908R, and 1007fs mutations represent 82% of the mutated chromosomes. The relative risk of developing CD in homozygous or compound heterozygous people has been estimated as between 10 and 40 times that of the general population. This high risk may support the opinion that CARD15/NOD2 variants are strong CD risk factors at the individual and population levels. SUBJECTS AND METHODS: The allele and genotype frequencies were calculated for the R702W, G908R, and 1007fs mutations in 3,575 Caucasian healthy controls recruited by 15 groups distributed on three continents. Geographic homogeneity was tested and the observed proportion of double mutants was compared with the expected value using χ2 tests. RESULTS: The allele frequencies of the R702W, G908R, and 1007fs mutations were 4.3% (3.6–4.9), 1.2% (0.8–1.6), and 2.3% (1.8–2.8), respectively, with large geographic fluctuations of the G908R, 1007fs, and wild-type alleles ( P < 0.0001). At the population level, no simple relationship was observed between mutation frequencies and the disease incidences in the studied populations. At the individual level, no significant deficit of double-dose mutation carriers among healthy controls was found, providing strong evidence that the penetrances of the most at-risk genotypes are low. CONCLUSION: Altogether, these data confirm that CARD15/NOD2 acts in interaction with other unknown risk cofactors.


Related Articles

  • Extreme heterogeneity in CARD15 and DLG5 Crohn disease-associated polymorphisms between German and Norwegian populations. Medici, Valentina; Mascheretti, Silvia; Croucher, Peter J. P.; Stoll, Monika; Hampe, Jochen; Grebe, Jochen; Sturniolo, Giacomo C.; Solberg, Camilla; Jahnsen, Jorgen; Moum, Bjorn; Schreiber, Stefan; Vatn, Morten H. // European Journal of Human Genetics;Apr2006, Vol. 14 Issue 4, p459 

    The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as...

  • Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease. Rigoli, Luciana; Romano, Claudio; Caruso, Rosario Alberto; Lo Presti, Maria A.; Di Bella, Chiara; Procopio, Vincenzo; Lo Giudice, Giuseppina; Amorini, Maria; Costantino, Giuseppe; Sergi, Maria D.; Cuppari, Caterina; Calabrò, Giovanna Elisa; Gallizzi, Romina; Salpietro, Carmelo Damiano; Fries, Walter; De Boer, Nanne K. H.; Kouroumalis, Elias A. // World Journal of Gastroenterology;7/28/2008, Vol. 14 Issue 28, p4454 

    AIM: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide polymorphisms (SNPs) of NOD2/CARD15 (R702W, G908R and L1007finsC), and Toll-like receptor 4 (TLR4) genes (D299G and T399I) in a selected...

  • Transmission of CARD15 (NOD2) Variants Within Families of Patients with Inflammatory Bowel Disease. Esters, Nele; Pierik, Marie; van Steen, Kristel; Vermeire, Severine; Claessens, Greet; Joossens, Sofie; Vlietinck, Robert; Rutgeerts, Paul // American Journal of Gastroenterology;Feb2004, Vol. 99 Issue 2, p299 

    OBJECTIVES: Three single nucleotide polymorphisms (SNPs) in CARD15 have been independently associated with Crohn's disease (CD). Since nothing is known about the transmission of these variants within families, this was the subject of our study in Flemish patients with inflammatory bowel disease...

  • Lack of evidence for association of primary sclerosing cholangitis and primary biliary cirrhosis with risk alleles for Crohn's disease in Polish patients. Gaj, Pawel; Habior, Andrzej; Mikula, Michal; Ostrowski, Jerzy // BMC Medical Genetics;2008, Vol. 9, Special section p1 

    Background: Numerous papers have addressed the association of mutations and polymorphisms of susceptibility genes with autoimmune inflammatory disorders. We investigated whether polymorphisms that confer susceptibility to Crohn's disease could be classified also as predisposing factors for the...

  • Tumor Necrosis Factor Receptor Superfamily, Member 1B Haplotypes Increase or Decrease the Risk of Inflammatory Bowel Diseases in a New Zealand Caucasian Population. Ferguson, Lynnette R.; Dug Yeo Han; Huebner, Claudia; Petermann, Ivonne; Barclay, Murray L.; Gearry, Richard B.; McCulloch, Alan; Demmers, Pieter S. // Gastroenterology Research & Practice;2009, Vol. 2009, Special section p1 

    Inflammatory bowel diseases (IBDs) comprising Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions with polygenic susceptibility. Interactions between TNF-alpha and TNF-alpha receptor play a fundamental role in inflammatory response. This study investigates the role...

  • Association of the organic cation transporter OCTN genes with Crohn's disease in the Spanish population. Martínez, Alfonso; del Carmen Martín, Maria; Mendoza, Juan L.; Taxonera, Carlos; Díaz-Rubio, Manuel; de la Concha, Emilio G.; Urcelay, Elena // European Journal of Human Genetics;Feb2006, Vol. 14 Issue 2, p222 

    The SLC22A4 and SLC22A5 genes within the IBD5 risk locus encode the organic cation transporters OCTN1 and OCTN2. Two variants, 1672C>T in SLC22A4 and −207G>C in SLC22A5, were shown to alter these genes' functions and were identified as genetic susceptibility factors for Crohn's disease...

  • Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn's disease in a New Zealand Caucasian cohort. Leung, Euphemia; Jiwon Hong; Fraser, Alan G.; Merriman, Tony R.; Vishnu, Prakash; Krissansen, Geoffrey W. // Immunology & Cell Biology;Apr2006, Vol. 84 Issue 2, p233 

    Polymorphisms in the organic cation transporter (OCTN) genes SLC22A4 (OCTN1; polymorphism 1672C/T) and SLC22A5 (OCTN2; polymorphism −207G/C) at the inflammatory bowel disease (IBD) 5 locus comprise a two-allele haplotype ( SLC22A-TC) associated with increased risk for Crohn's disease (CD)....

  • NOD2 mutations and Crohn's disease: are Paneth cells and their antimicrobial peptides the link? Grimm, M. C.; Pavli, P. // Gut;Nov2004, Vol. 53 Issue 11, p1558 

    The article examines if there is an association of Paneth cells and their antimicrobial peptides in NOD2 mutations and Crohn's disease. According to the authors, there is manifestation that NOD2 variants in Crohn's disease are associated with atrophied mucosal Α-defensin production, leading...

  • Trial Protocol: Communicating DNA-based risk assessments for Crohn's disease: a randomised controlled trial assessing impact upon stopping smoking. Whitwell, Sophia C. L.; Mathew, Christopher G.; Lewis, Cathryn M.; Forbes, Alastair; Watts, Sally; Sanderson, Jeremy; Hollands, Gareth J.; Prevost, A. Toby; Armstrong, David; Kinmonth, Ann Louise; Sutton, Stephen; Marteau, Theresa M. // BMC Public Health;2011, Vol. 11 Issue 1, p44 

    Background: Estimates of the risk of developing Crohn's disease (CD) can be made using DNA testing for mutations in the NOD2 (CARD15) gene, family history, and smoking status. Smoking doubles the risk of CD, a risk that is reduced by stopping. CD therefore serves as a timely and novel paradigm...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics