Prevalence of CARD15/NOD2 Mutations in Caucasian Healthy People View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-06

AUTHORS

Jean-Pierre Hugot, Isabelle Zaccaria, Juleen Cavanaugh, Huiying Yang, Sverine Vermeire, Maarit Lappalainen, Stefan Schreiber, Vito Annese, Derek P Jewell, Elizabeth V Fowler, Steven R Brant, Mark S Silverberg, Judy Cho, John D Rioux, Jack Satsangi, Miles Parkes

ABSTRACT

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 chi2 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. More... »

PAGES

ajg2007243

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1111/j.1572-0241.2007.01149.x

    DOI

    http://dx.doi.org/10.1111/j.1572-0241.2007.01149.x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001274568

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17319929


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