Prevalence of CARD15/NOD2 mutations in caucasian healthy people

Hugot, Jean-Pierre, Zaccaria, Isabelle, Cavanaugh, Juleen, Yang, Huiying, Vermeire, Sverine, Lappalainen, Maarit, Schreiber, Stefan, Annese, Vito, Jewell, Derek P., Fowler, Elizabeth V., Brant, Steven R., Silverberg, Mark S., Rioux, John D., Satsangi, Jack, Parkes, Miles and IBD International Genetics Consortium (2007) Prevalence of CARD15/NOD2 mutations in caucasian healthy people. The American Journal of Gastroenterology, 102 2: 1259-1267. doi:10.1111/j.1572-0241.2007.01149.x

Author Hugot, Jean-Pierre
Zaccaria, Isabelle
Cavanaugh, Juleen
Yang, Huiying
Vermeire, Sverine
Lappalainen, Maarit
Schreiber, Stefan
Annese, Vito
Jewell, Derek P.
Fowler, Elizabeth V.
Brant, Steven R.
Silverberg, Mark S.
Rioux, John D.
Satsangi, Jack
Parkes, Miles
IBD International Genetics Consortium
Title Prevalence of CARD15/NOD2 mutations in caucasian healthy people
Journal name The American Journal of Gastroenterology   Check publisher's open access policy
ISSN 0002-9270
Publication date 2007-06
Sub-type Article (original research)
DOI 10.1111/j.1572-0241.2007.01149.x
Volume 102
Issue 2
Start page 1259
End page 1267
Total pages 9
Place of publication New York, U.S.
Publisher Blackwell Publishing
Language eng
Subject 11 Medical and Health Sciences
1103 Clinical Sciences
Formatted 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.
Keyword Crohn's Disease
Public Health
Caucasian Population
Clinical studies
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 78 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 07 Jan 2010, 12:33:39 EST by Ms May Balasaize on behalf of Faculty Of Health Sciences