Table of Contents 21-1

Crohn’s Disease, Genotype and Growth

The authors studied the role of NOD2 genotype on disease location and severity and on growth retardation. Genotyping for 3 NOD2 single nucleotide polymorphism was performed in 93 patients who had detailed growth records and disease assessments. Effects on z scores for height and weight were assessed. NOD2 mutations were found in 35% of patients; these mutations correlated with an ileal location of the illness. Height retardation, both at the onset and at follow up, was also associated with an ileal localization of the disease. Use of steroids and immunosuppressant therapy also affected growth. However the degree of disease severity was the strongest association with impaired growth, height and weight failure odd ratios were 6.12 and 4.5 respectively. NOD2 genotype was not correlated with growth retardation.

Wine E, Reif SS, Leshinsky-Silver E, et al. Pediatric Crohn’s disease and growth retardation: the role of genotype, phenotype and disease severity. Pediatrics 2004;114:1281-6.

Editor’s Comment: The first disease associated mutations for Crohn’s disease were found in the NOD2/CARD15 gene located in the paracentric region of chromosome 16.^1-3 There were 3 loci identified as independent risk factors for the development of the illness. These mutations were not directly correlated with the presence of growth retardation, a manifestation of Crohn’s disease that affect up to one-third of the patients. NOD2 mutations were related to disease location, and they were present in 43% of patients who had ileal involvement. These children had height retardation when the disease was diagnosed and it persisted during follow-up. Other studies have also implicated NOD2 mutations with growth retardation.⁴ Short stature and poor growth in Crohn’s disease is known to be primarily the result of inadequate nutrition due to anorexia and postprandial pain leading to poor intake, compounded by malabsorption and by other factors such as steroid treatment. Improvement usually follows nutritional rehabilitation. The genotype may affect growth through NOD2 mutations which determine the disease location and severity.

Fima Lifshitz, MD

References - (linked to )

1. Hugot JP, Chamaillard M, Zouali H, et al. Nature 2001;411:599-603.
2. Ogura Y, Bonen DK, Inohara N, et al. Nature 2001;411:603-6.
3. Hampe J, Cuthbert A, Croucher PJ, et al. Lancet 2001;357:1925-8.
4. Lesage S, Zouali H, Cezard JP, et al. Am J Hum Genet 2002;70:845-57.