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• W163310463 abstract "Genetic studies can be greatly aided by the use of subclinical markers that are closer to the basic defect and thus likely to detect more individuals with the abnormal genotype. At least two approaches are generally used to characterize subclinical markers. One is the family study approach. The detection of subclinical abnormalities in unaffected relatives similar to those found in the probands can distinguish between an inherited predisposition and a secondary abnormality due to the disease process. The second approach is the combination of subclinical marker with genetic marker studies. Specific association of a subclinical marker with a genetic marker indicates genetic determination of the subclinical marker. The identification of a genetically determined subclinical marker can help to define a more homogeneous disease group for genetic studies. The most studied subclinical markers in inflammatory bowel disease (IBD) are antineutrophil cytoplasmic antibodies (ANCAs) for ulcerative colitis (UC) and intestinal permeability for Crohn's disease (CD). Even so, for these as well as several other promising subclinical markers, there is an obvious need for more twin, family and genetic marker studies. An elevated intestinal permeability in a proportion of unaffected relatives of CD patients has been observed in the majority of family studies. ANCAs, a highly specific marker for UC, have been found with a significantly increased prevalence in unaffected relatives of UC patients compared with spouses of the patients. Moreover, the distribution of the ANCAs is familial rather than random, suggesting heterogeneity within UC. In combination with genetic marker studies (human leukocyte antigen [HLA] class II genes), the authors observed a differential association: ANCA-positive UC was associated with DR2, while ANCA-negative UC associated with DR4. These data lead to the conclusion that the heterogeneity indicated by ANCA is genetically determined and that this genetic heterogeneity should be taken into consideration in future genetic, clinical and pathophysiological studies. In the aggregate, these data indicate that the subclinical marker approach is a powerful means for demonstrating genetic and etiological heterogeneity, and can be an important tool to define the etiology and natural history of the various diseases that make up IBD." @default.
• W163310463 created "2016-06-24" @default.
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• W163310463 date "1995-01-01" @default.
• W163310463 modified "2023-10-16" @default.
• W163310463 title "Subclinical Markers of Human Inflammatory Bowel Disease" @default.
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• W163310463 doi "https://doi.org/10.1155/1995/456197" @default.
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