The contribution of the DLG5 113A variant in early-onset inflammatory bowel disease

J Pediatr. 2007 Mar;150(3):268-73. doi: 10.1016/j.jpeds.2006.12.010.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease / epidemiology*
  • Heterozygote
  • Humans
  • Incidence
  • Inflammatory Bowel Diseases / epidemiology*
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / physiopathology
  • Logistic Models
  • Male
  • Membrane Proteins / genetics*
  • Mutation, Missense*
  • Odds Ratio
  • Pedigree
  • Phenotype
  • Probability
  • Prognosis
  • Scotland / epidemiology
  • Severity of Illness Index
  • Tumor Suppressor Proteins / genetics*

Substances

  • DLG5 protein, human
  • Membrane Proteins
  • Tumor Suppressor Proteins