Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives?
OBJECTIVE
One approach to unraveling the genetics of complex inherited disease, such as Crohn's disease, is to search for subclinical disease markers among unaffected family members. We assessed the possible presence, prevalence, and inheritance pattern of subclinical intestinal inflammation in apparently healthy relatives of patients with Crohn's disease.


METHODS
A total of 49 patients with Crohn's disease, 16 spouses, and 151 (58%) of 260 available first-degree relatives underwent a test for intestinal inflammation (fecal calprotectin concentration). The mode of inheritance was assessed from 36 index patients (by variance component analysis) when more than 50% of relatives were studied.


RESULTS
Fecal calprotectin concentrations in patients with Crohn's disease (47 mg/L; confidence interval [CI], 27-95 mg/L) and relatives (11 mg/L; CI, 9-14 mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; CI, 3-5 mg/L), whereas that of the spouses did not (4 mg/L; CI, 3-6 mg/L; P > 0.5). Fecal calprotectin concentration was increased in 49% of all relatives studied. The increased fecal calprotectin concentration among the relatives of the 36 index patients had an inheritance pattern that was most consistent with an additive inheritance pattern.


CONCLUSIONS
There is a high prevalence of subclinical intestinal inflammation in first-degree relatives of patients with Crohn's disease that conforms best to an additive inheritance pattern. The genetic basis for this abnormality may represent a risk factor for Crohn's disease.
Thjodleifsson
Bjarni
B
Department of Medicine, Iceland University Hospital, Reykjavik, Iceland.
Sigthorsson
Gudmundur
G
Cariglia
Nick
N
Reynisdottir
Inga
I
Gudbjartsson
Daniel F
DF
Kristjansson
Kristleifur
K
Meddings
Jonathan B
JB
Gudnason
Vilmundur
V
Wandall
Johan H
JH
Andersen
Leif Percival
LP
Sherwood
Roy
R
Kjeld
Matthias
M
Oddsson
Einar
E
Gudjonsson
Hallgrimur
H
Bjarnason
Ingvar
I
D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015995:Prevalence
D039841:Leukocyte L1 Antigen Complex