MedWire News: Crohn's disease (CD) patients who carry two mutant NOD2 alleles may be at high risk for future disease complications, namely strictures and fistulae, according to results from a meta-analysis of genetic studies.

"Targeted early-intensive therapy for high-risk patients with two NOD2 mutations might be beneficial, if prospective trials can demonstrate changes in the natural history in this subset of patients," comment Jeremy Adler (University of Michigan Health System, Ann Arbor, USA) and team.

The researchers say another major finding of the meta-analysis is "the lack of prognostic value of the presence of one mutant allele for predicting CD behavior... It is likely that the level at which genetics contributes to phenotypic disease expression is complex and multiple risk alleles contribute to complex interactions."

The meta-analysis included 49 studies in which the presence of (current or past) stricturing or fistulizing was assessed among 8893 CD patients with median disease durations varying from 3.9 to 16.5 years.

All patients underwent genotyping and 2897 were found to have at least one mutant NOD2 allele.

Writing in the American Journal of Gastroenterology, the team reports that the presence of one NOD2 mutant allele was associated with a disease complication risk of 8%, which rose to 41% in the presence of two mutant alleles.

Adler and colleagues also found that two mutant alleles predicted the occurrence of future CD complication with a high specificity of 98%, but a sensitivity of 11% and an area under the receiver operating characteristic curve of 0.56, which both reflect low diagnostic accuracy.

Of note, no significant association was found between NOD2 mutations and the risk for perianal disease, but the risk for CD-related surgery was 58% higher among patients with at least one mutant NOD2 allele compared with those with no mutant forms of the allele.

Adler et al say that further study into methods of preventing CD complications is required. They add that high-risk CD patients with two NOD2 mutations may form a useful subgroup for such analyses.

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