The Contribution of the DLG5 113A Variant in Early-Onset Inflammatory Bowel Disease
Received 14 July 2006; received in revised form 4 October 2006; accepted 7 December 2006.
Objective
To assess the contribution of the 113 G→A missense mutation within the discs, large homolog 5 (DLG5) gene in childhood-onset inflammatory bowel disease (IBD) in Scotland.
Study design
Two-hundred and ninety-six children with IBD were studied. Parental DNA was also collected for transmission disequilibrium testing (TDT) analysis. Genotyping was performed by TaqMan®. Genotype-phenotype analysis was also undertaken. Socioeconomic status was assigned using a deprivation category (DepCat) score 1 through 7 (1 = most affluent).
Results
TDT analysis demonstrated a significant association with IBD (P = .045). On unifactorial analysis, 113A carriage was associated with: (1) higher social class (DepCat 1 compared with 2-7, and 1-2 compared with 3-7) (66.7% vs 22.6%, P = .0005, OR 6.84 [1.99-23.55] and 37.2% vs 22.2%, P = .03, OR 2.08 [1.04-4.17], respectively); (2) higher height centile (>75th centile vs <75th centile) (42.9% vs 23.1%, P = .01, OR 2.50 [1.18-5.28]); and (3) male sex in Crohn’s disease (CD) (29.3% vs 16.9%, P = .04, OR 2.04 [1.01-4.11]). Multifactorial analysis demonstrated that higher social class (DepCat 1) was independently associated with carriage of variants of 113A (P = .001, OR=6.92 [2.24-21.33]).
Conclusions
DLG5 113A is associated with increased susceptibility to IBD in Scottish children. The effect may be most marked for those children living in relative affluence.
⁎Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, Edinburgh, United Kingdom
†Public Health Sciences, Edinburgh University, Edinburgh, United Kingdom
‡Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, United Kingdom
§Department of Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom
∥Department of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, United Kingdom
¶Department of Child Health, University of Glasgow, Glasgow, United Kingdom
⁎⁎Department of Paediatric Gastroenterology, Royal Aberdeen Children’s Hospital, Aberdeen, United Kingdom.
Reprint requests: Dr R. K. Russell, MRCPCH, Gastrointestinal Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU.
The University of Edinburgh Medical Faculty Fellowship funds R.K.R. This study is supported by a Wellcome Trust Programme Grant (072789/Z/03/Z) with additional support from Schering Plough and the GI/Nutrition research fund, Child Life and Health, University of Edinburgh.
ABSTRACT