TY - JOUR
T1 - Subclinical intestinal inflammation
T2 - An inherited abnormality in Crohn's disease relatives?
AU - Thjodleifsson, Bjarni
AU - Sigthorsson, Gudmundur
AU - Cariglia, Nick
AU - Reynisdottir, Inga
AU - Gudbjartsson, Daniel F.
AU - Kristjansson, Kristleifur
AU - Meddings, Jonathan B.
AU - Gudnason, Vilmundur
AU - Wandall, Johan H.
AU - Andersen, Leif Percival
AU - Sherwood, Roy
AU - Kjeld, Matthias
AU - Oddsson, Einar
AU - Gudjonsson, Hallgrimur
AU - Bjarnason, Ingvar
N1 - Funding Information: Supported in part by a Biomedical Research Collaboration grant from the Wellcome Trust (ref. 048461).
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Background & Aims: 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 [Cl], 27-95 mg/L) and relatives (11 mg/L; Cl, 9-14 mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; Cl, 3-5 mg/L), whereas that of the spouses did not (4 mg/L; Cl, 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.
AB - Background & Aims: 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 [Cl], 27-95 mg/L) and relatives (11 mg/L; Cl, 9-14 mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; Cl, 3-5 mg/L), whereas that of the spouses did not (4 mg/L; Cl, 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.
UR - https://www.scopus.com/pages/publications/0038724272
U2 - 10.1016/S0016-5085(03)00383-4
DO - 10.1016/S0016-5085(03)00383-4
M3 - Article
C2 - 12806605
SN - 0016-5085
VL - 124
SP - 1728
EP - 1737
JO - Gastroenterology
JF - Gastroenterology
IS - 7
ER -