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22-04-2010 | Gastroenterology | Article

NOD2 gene variants not associated with Crohn’s disease


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MedWire News: A large Danish study has argued against screening for Crohn’s disease in the general population using three genetic variants, despite positive findings in earlier case–control investigations.

Research in more than 43,000 Danes showed no significant association between Crohn’s disease and specific variants on the nucleotide-binding oligomerization domain containing gene (NOD2), also known as the caspase recruitment domain gene CARD15.

The fraction of Danes with these genetic variants who developed Crohn’s disease by the time they were middle-aged, was also lower than predicted by earlier studies.

Investigators genotyped 43,596 people in Denmark for the NOD2 single nucleotide polymorphisms Arg702Trp (rs2066844) and Gly908Arg (rs2066845) and the frame-shift mutation Leu1007fsinsC (rs5743293).

Overall, 89% of participants did not carry the risk associated alleles, 11% were heterozygotes, and 0.4% were compound heterozygotes or homozygotes.

The odds ratio (OR) for Crohn's disease in heterozygotes versus noncarriers was not statistically significant at 1.2, compared with a significant aggregated OR of 2.4 in a recent meta-analysis of case-control studies.

The OR for compound heterozygotes and homozygotes combined versus noncarriers was again statistically insignificant at 3.3 in the Danish study, compared with a significant OR of 17.0 in the meta-analysis.

Crohn’s disease was diagnosed in just two Danish compound heterozygotes and no homozygotes. The penetrance at age 50 years of NOD2 genetic variants of Crohn's disease was 0.30% for heterozygotes and 1.50% for compound heterozygotes and homozygotes.

Reporting in the Canadian Medical Association Journal, Børge Nordestgaard (Copenhagen University Hospital, Denmark) and colleagues say different results to case–control studies may occur from comparing patients at a hospital clinic to the general population.

Nonetheless, they conclude: “The low penetrance of the NOD2 genetic variants in the general population documented in our study suggests that these genetic variants should not be considered as a genetic test for screening individuals in the general population.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Anita Wilkinson