Subclinical intestinal inflammation: An inherited abnormality in Crohn's disease relatives?

Bjarni Thjodleifsson, Gudmundur Sigthorsson, Nick Cariglia, Inga Reynisdottir, Daniel F. Gudbjartsson, Kristleifur Kristjansson, Jonathan B. Meddings, Vilmundur Gudnason, Johan H. Wandall, Leif Percival Andersen, Roy Sherwood, Matthias Kjeld, Einar Oddsson, Hallgrimur Gudjonsson, Ingvar Bjarnason*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1728-1737
Number of pages10
Issue number7
Publication statusPublished - 1 Jul 2003

Bibliographical note

Funding Information:
Supported in part by a Biomedical Research Collaboration grant from the Wellcome Trust (ref. 048461).


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