primary prevention of coeliac disease - Associazione Italiana ...

COELIAC DISEASE IN THE SAHARAWI
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confirmation of the reliability of the CD diagnosis (based on both the serum EMA
testing and the small intestinal biopsy) in these North African children. Most
importantly, these results are also clear evidence that CD has a similar HLA association
in distantly related populations. The aetiological mechanism of the class II association
involves binding and T cell recognition of gluten derived peptides deaminated in the
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small intestine by the enzyme tissue transglutaminase , and these properties of class II
molecules are very likely conserved among different ethnic groups.
In a manner consistent with the high disease prevalence, the main CD susceptibility
haplotype DQA1*0501-DQB1*0201, detected nearly always within a DR3 haplotype,
exhibited one of the highest frequencies in the world in the general background
Saharawi population. This could partially explain the very high CD prevalence
observed in the Saharawi population. However, it should be noted that a similar
frequency of DQA1*0501-DQB1*0201 has been found also in other populations, such
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as the Sardinians where the disease is around 5 times less frequent (1%) . Our results
therefore suggest that other non-DQ genes or environmental factors are also operative
in determining the high CD prevalence observed in the Saharawi.
From an evolutionary perspective, such disease frequency might be related to the
high prevalence of genes such as the Dq2, that have been selectively neutral or even
beneficial for several hundred generations, that became disadvantageous following
quick and dramatic changes of the environmental context in which the Saharawis lived.
In the traditional Saharawi diet, the intake of gluten was very low and its introduction
usually occurred after the second or third year of life. During the last century, in a span
of few generations, wheat-based products, especially bread, have become the staple
food after the Spanish colonization. Nowadays, gluten is introduced early in the
Saharawi infant's diet, occasionally as early as the first month of life. Since in CD the
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degree of intestinal mucosal damage is related to the amount of ingested gluten , the
enteropathy of the “ancestral” CD-prone individuals was presumably milder. As such,
in terms of genetic fitness, it did not represent a major selective disadvantage or might
have even exerted some protective effect against intestinal infections because a
moderately atrophic jejunal mucosa partially lacks the membrane receptors required
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for microorganisms adhesion . Moreover, a mild CD and the accompanying small
degree of inflammation of the jejunal mucosa, can also provide a source of reactive
lymphomonocytes, thus further increasing the protective effect against intestinal
infections. In contrast, the severe celiac enteropathy currently found in Saharawi
children is associated with an early and high gluten intake and it is no longer neutral or
“protective” but instead harmful, as it causes early intestinal malabsorption and
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malnutrition, potentially leading to death .
From these data a more general theory can be proposed. High disease frequency of a
complex trait in a given population might be related to the high prevalence of genes that
have been selectively neutral or even beneficial for several hundred generations, but
became disadvantageous following quick changes of the environment. According to
this interpretation, complex traits can be regarded as “residual traits“ caused by
dramatic transformations of the environmental context in which a given population
used to live across evolutionary time periods. Some environmental transformations can
occur too quickly to be accompanied by changes in the genetic structure of the human
populations. Indeed, the evolutionary time periods necessary to modify the genetic