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


METHODS
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.
Russell
R K
RK
Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, Edinburgh, United Kingdom. richardkrussell71@hotmail.com
Drummond
H E
HE
Nimmo
E R
ER
Anderson
N
N
Wilson
D C
DC
Gillett
P M
PM
McGrogan
P
P
Hassan
K
K
Weaver
L T
LT
Bisset
W M
WM
Mahdi
G
G
Satsangi
J
J
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D011336:Probability; D011379:Prognosis; D012606:Scotland / Q000453:epidemiology; D012720:Severity of Illness Index; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C114461:DLG5 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins