Gastroenterology

Gastroenterology

Volume 124, Issue 7, June 2003, Pages 1728-1737
Gastroenterology

Clinical-alimentary tract
Subclinical intestinal inflammation: an inherited abnormality in Crohn’s disease relatives?

https://doi.org/10.1016/S0016-5085(03)00383-4Get rights and content

Abstract

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 [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.

Section snippets

Patients and methods

Forty-nine patients with Crohn’s disease, which represents just <30% of all patients with Crohn’s disease in Iceland, were approached for these studies by mail and telephone, and all participated. Thirty-four of these patients were seen by 3 gastroenterologists (representing >80% of those under their care) at Reykjavik University Hospital, which provides acute medical service along with Reykjavik Hospital to the greater Reykjavik area (on the southwest coast with a population of 140,000). This

Intestinal inflammation in patients with Crohn’s disease and relatives

The calprotectin values in patients with Crohn’s disease (47 mg/L; CI, 27–95 mg/L) and their first-degree relatives (11 mg/L; CI, 9–14 mg/L) differed significantly (P < 0.0001) from controls (median, 4 mg/L; CI, 3–5 mg/L). There was no significant difference between fecal calprotectin concentrations in spouses (4 mg/L; CI, 3–6 mg/L) and controls. Figure 1 shows the data graphically.

Forty-three (88%) of the 49 patients with Crohn’s disease, 74 (49%) of the 151 first-degree relatives, and 2

Discussion

This study shows increased fecal calprotectin concentrations, indicative of subclinical intestinal inflammation, in 49% of the first-degree relatives of patients with Crohn’s disease. Of the models tested, the pattern of inheritance of elevated calprotectin concentrations among the relatives of patients with Crohn’s disease is most consistent with an additive model. This suggests that the abnormality responsible for this observation may represent a genetically determined (subclinical disease)

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