primary prevention of coeliac disease - Associazione Italiana ...

COELIAC DISEASE IN THE SAHARAWI
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ASP families, for instance in a consortium type study addressed to analyse all the CD
ASP collectable worldwide on the order of 2,000 or more (ASPs). However, this
strategy based on the analysis of very large sample sets of ASP families that have to be
necessarily collected from different populations cannot provide a significant benefit
regarding the confounding effects of genetic heterogeneity. An alternative approach
could be to concentrate on an isolated population showing an high disease prevalence,
to reconstruct all the relationships between the various affected cases and scan with
parametric and non-parametric linkage tests the whole genome to detect non-HLA gene
effects. It is likely that such a study design, already applied in the case of type 1
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diabetes , would provide sufficient statistical power to detect significant results across
the genome.
The high prevalence of CD in the Saharawi population
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CD is typically found in individuals of Caucasian origin . In Europe and North
15-16
America the disease prevalence is around 0.5-1 % of the general population .
Recently a tenfold higher CD frequency (5.6 %) was reported in the Saharawi, a people
of Arab and Berber origin with high degree of consanguinity, living in the Sahara desert
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. We analysed the genetic association of the main CD locus in a group of Saharawi
children affected with CD and their first-degree relatives. The aims of this study (which
is described in details below) were:
1) to evaluate whether the degree of association at the main disease locus was similar to
that observed in other populations;
2) to investigate how the frequency of the predisposing HLA molecules in the general
Saharawi population relates to the high prevalence observed in this ethnic group.
Patients and methods
This work was performed on Saharawi refugees living in the camps near Tindouf,
Algeria. Blood samples were collected with the informed consent from a group of
previously diagnosed subjects with CD and their first-degree relatives. The diagnosis of
CD was based on the finding of serum IgA class antiendomysium antibodies (EMA)
positivity on at least two consecutive blood samples and, in a subgroup of patients, the
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typical enteropathy at the small intestinal biopsy, as previously described . EMA were
detected by indirect immunofluorescence on serum diluted both 1:5 and 1:50, using
monkey oesophagus as the antigenic substrate (Antiendomisio Eurospital, Trieste,
Italy). Patients were 79 subjects (33 males and 44 females) deriving from 69
independent families, with a median age of 8 years (range: 2-37) and including 69
probands, 8 siblings and 2 mothers. Overall 136 healthy subjects were also investigated
with a median age of 30 years, range 2-70 years. These included 29 individuals from 9,
non-CD, unrelated families and 107 first-degree relatives of the CD patients (53
mothers, 17 fathers and 37 siblings). Additionally, in 12 parents of CD patients for
which DNA samples were not available, the DQ genotypes were unequivocally
deduced based on the available data from the other parent and the offsprings.
DNA was extracted using the chelex method starting from dried blood spots
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(Guthrie cards) . Amplification of the polymorphic second exon of the HLA-DRB1,