primary prevention of coeliac disease - Associazione Italiana ...

Catassi C, Fasano A, Corazza GR (eds):
Primary prevention of coeliac disease. The
utopia of the new millennium? Perspectives on
Coeliac Disease, vol. 1, AIC Press, pp 31-41
The association of the HLA-DQ molecules with
coeliac disease in the Saharawi: an evolutionary
perspective
1 2
Francesco Cucca and Carlo Catassi
1
Department of Biomedical and Biotechnologies Sciences, University of Cagliari,
2
Cagliari, Italy. Department of Pediatrics , University of Ancona, Ancona, Italy.
The familial clustering of CD
Coeliac disease (CD) is an immune-mediated enteropathy caused by the ingestion
of wheat and other gluten-containing cereals (rye, barley) in genetically predisposed
1
individuals . CD is strongly clustered in families as illustrated by the sibling lifetime
2-3
risk/population prevalence ratio, lequal s to 30-60 in different studies . These
epidemiological observations indicate the strong influence of genetic factors in the
disease predisposition. This is also strongly suggested by the recurrence risk of 70-
4
100% observed in monozygotic twins (MZ) . Twin studies are particularly important
for human geneticists because the risk in MZ twins provides a direct estimate of
penetrance (the effect of the genotype on the phenotype) for the whole complement of
susceptibility alleles at multiple loci. While it is necessary to extend these preliminary
studies in larger cohorts of twins, the fact that the recurrence risk might not be 100%,
and thus that the penentrance is incomplete, might indicate that other modifying
epigenetic factors, such as the stochastic rearrangements of the T-cell receptor, and/or
other environmental factors (in addition to the gluten in the diet) could also be involved
in CD.
The contribution of genes located in the HLA region to CD predisposition
The major histocompatibility complex (MHC) human leukocyte antigen (HLA)
region on chromosome 6p21 contains the major and, so far, the only consistently
confirmed genetic component for CD predisposition. The HLA/MHC contains a
densely packed array of at least 150 genes in 3,500 kb of DNA. Proteins encoded within
the HLA region determine the way in which antigens are processed, translocated and
presented to T-lymphocytes. During development of the T cell repertoire, HLA class I
and class II molecules control positive and negative selection of the T-lymphocytes in
the thymus. Not surprisingly, therefore, genes in the HLA region influence
susceptibility to a large number of disorders, particularly autoimmune diseases.
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