Clustering of increased small intestinal permeability in families with Crohn's disease.
OBJECTIVE
Small intestinal permeability is increased in a proportion of patients with Crohn's disease (CD) and a subset of their healthy relatives. A primary permeability defect was postulated in the pathogenesis of the disease. The aim of this study was to identify a possible genetic pattern in the distribution of CD and/or abnormal permeability.


METHODS
Differential urinary excretion of lactulose and mannitol (L/ M) in complete CD families was determined. Controls included healthy families and families with ulcerative colitis. Pedigrees were used to compare the distribution of CD and/or increased permeability.


RESULTS
The L/M was significantly increased in patients with CD. Seventeen of 67 first-degree relatives (25%) had a ratio greater than the upper limit (P95 = 0.0170). Permeability results of CD families showed a highly significant familial aggregation. The lack of a genetic pattern in relation with CD and occurrence of disturbed permeability especially within generation, points toward a shared environmental factor. Five of 14 healthy spouses (36%) of patients with CD had also an increased permeability, and prevalence of increased permeability was not higher in families with known familial occurrence (P = 0.85).


CONCLUSIONS
This large family study confirms an increased permeability in a subset of healthy relatives of patients with CD. However, the absence of a typical family pattern and the high prevalence in spouses is in favor of a common nongenetic factor or a subclinical disease manifestation.
Peeters
M
M
Center for Gastrointestinal Research, Leuven, Belgium.
Geypens
B
B
Claus
D
D
Nevens
H
H
Ghoos
Y
Y
Verbeke
G
G
Baert
F
F
Vermeire
S
S
Vlietinck
R
R
Rutgeerts
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism*; D007792:Lactulose / Q000652:urine; D008297:Male; D008353:Mannitol / Q000652:urine; D008875:Middle Aged; D010375:Pedigree; D010539:Permeability; D012016:Reference Values
D008353:Mannitol; D007792:Lactulose