NOD2 mutations predict risk for surgery in pediatric CD patients
MedWire News: Individuals with pediatric-onset Crohn's disease (CD) who carry risk-associated alleles of three NOD2 gene variants are more likely to require surgery at an earlier stage than are noncarriers, show study findings published in the Journal of Pediatric Surgery.
The three NOD2 variants - p.Arg702Trp, p.Gly908Arg, and p.1007fs - have previously been shown to be associated with CD, ileal disease location, and fibrostenosis, although some other results have been conflicting, as reported by MedWire News.
In this study, Martin Lacher (University of Munich, Germany) and colleagues assessed the effect of NOD2 genotype on disease manifestation and risk for surgery in 171 German children with CD, aged 11.8 years on average. A group of 253 adults undergoing inguinal hernia repair were also genotyped for comparison purposes (controls).
Lacher and team found that 45.6% of the children were carriers of at least one risk-associated allele for the three variants, compared with only 14.2% of the control group. Indeed, presence of one or more of the risk-associated genotypes was significantly associated with CD.
"Collectively, our data suggest that nearly every second German child with CD is a carrier of at least one of the three common NOD2 mutations," say the researchers.
In addition, those with the risk-associated genotype for p.1007fs were a significant 4.73-fold more likely to have isolated ileal disease and 9.80-fold more likely to develop strictures than were noncarriers.
Overall, 18.7% of the children needed intestinal resection at a mean age of 14.9 years. Stricturing is strongly linked to requirement for surgery in CD patients, so the investigators assessed possible links between p.1007fs genotype and need for surgery.
They found that children with the risk-associated p.1007fs genotype had a mean time to surgery of 2.2 years, compared with 4.0 years for those without.
"Our data suggest that the three common NOD2 mutations confer susceptibility to CD in German children," write the authors. "Especially, the p.1007fs mutation increases the likelihood of fibrostenotic behavior in early onset CD, which often requires surgical resection."
They conclude: "Thus, genotyping may identify children who are at an increased risk for an aggressive clinical course."
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By Helen Albert