Pediatric Crohn's disease and growth retardation: the role of genotype, phenotype, and disease severity.
BACKGROUND
Delayed growth is a well-established feature of pediatric Crohn's disease. Several factors have been shown to affect growth, including disease location, severity, and treatment. The recently discovered NOD2 gene has been correlated to ileal location of Crohn's disease and subsequently could affect growth through the resulting phenotype or as an independent risk factor. The aim of our study was to determine if growth retardation is affected by genotype independently of disease location or severity.


METHODS
Genotyping for 3 NOD2 single-nucleotide polymorphisms was performed in 93 patients with detailed growth records. Parameters including disease location, disease severity, and NOD 2 genotype and their effect on z scores for height and weight at disease onset and during follow-up were analyzed.


RESULTS
NOD2 mutations were correlated with ileal location but not with disease severity or growth retardation. Ileal involvement was significantly associated with height retardation at disease onset and the lowest z score during follow-up. Use of steroids affected weight but not height. Regression models for growth variables revealed that the strongest association with impaired growth is with disease severity (weight- and height-failure odds ratios: 6.17 and 4.52, respectively).


CONCLUSIONS
Severity of disease is correlated with growth failure for both height and weight. Location of disease is a weaker predictor of disordered growth and is correlated with growth retardation but not growth failure. The NOD2 genotype was not correlated with growth retardation or growth failure.
Wine
Eytan
E
Pediatric Gastroenterology and Nutrition Unit, E. Wolfson Medical Center, Holon, Israel.
Reif
Shimon S
SS
Leshinsky-Silver
Esther
E
Weiss
Batya
B
Shaoul
Ron R
RR
Shamir
Raanan
R
Wasserman
Dror
D
Lerner
Aaron
A
Boaz
Mona
M
Levine
Arie
A
D002648:Child; D003424:Crohn Disease / Q000145:classification / Q000150:complications / Q000235:genetics*; D005838:Genotype; D006130:Growth Disorders / Q000209:etiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016015:Logistic Models; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein