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 24 November 2017

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News

Genetic variants predict pediatric Crohn's characteristics

NOD2/CARD15 variants are strongly associated with several markers of disease severity in pediatric Crohn's disease, notably need for surgery, finds the latest issue of Inflammatory Bowel Diseases.

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The incidence of early-onset Crohn's disease in Scotland is among the highest worldwide.

There are 3 single nucleotide polymorphisms R702W, G908R and Leu1007finsC in the NOD2/CARD15 gene that predispose to adult Crohn's.

Dr Richard Russell and colleagues investigated the impact of these variants to disease susceptibility.

The research team also assessed the impact of the variants on the phenotype in the Scottish early-onset inflammatory bowel disease (IBD) population.

The team genotyped 906 individuals including 247 Scottish IBD patients aged under 16 years at diagnosis, and 414 parents with 245 controls.

Transmission disequilibrium testing, case-control analysis and detailed genotype-phenotype analysis were performed.

The team found that Leu1007finsC variant was associated with susceptibility to Crohn's by case-control, and transmission disequilibrium testing.

Lower weight/height centile was associated with NOD2/CARD15 variants
Inflammatory Bowel Diseases

The Population Attributable Risk for the 3 NOD2/CARD15 mutations was 8%.

The researchers noted that carriage of NOD2/CARD15 variants was associated with, at diagnosis, decreased albumin, and raised C-reactive protein.

At follow up, the researchers observed that carriage of NOD2/CARD15 variants was associated with the need for surgery, and jejunal involvement.

Jejunal and ileal involvement, raised C-reactive protein, lower weight/height centile, and stricturing disease were associated with NOD2/CARD15 variants.

In addition, the team demonstrated with multifactorial analysis that carriage was associated with need for surgery.

Dr Russell's team concluded, “These NOD2/CARD 15 variants in the Scottish early onset Crohn's disease population have a definite, albeit relatively small contribution to Crohn's disease susceptibility but a major impact on phenotype.”

“In particular NOD2/CARD15 variants are strongly associated with several markers of disease severity in pediatric Crohn's disease, notably need for surgery.”

Inflamm Bowel Dis 2005: 11(11): 955-64
26 October 2005

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