In Europe and the USA, the mean frequency of celiac disease (CD) in the general population is approximately 1%, with some regional differences, the reasons for which remain elusive. A similar disease prevalence has been found in other countries mostly populated by individuals of European origin, e.g. Australia and Argentina. In Western countries, a true rise in overall CD prevalence of CD has been documented. CD is a common disorder in North Africa, the Middle East and India; however, the diagnostic rate is low in these countries due to low availability of diagnostic facilities and poor disease awareness. The highest CD prevalence in the world (5.6%) has been described in an African population originally living in Western Sahara, the Saharawi, of Arab-Berber origin. The reasons for this high CD frequency are unclear but could be primarily related to recent dietary changes and genetic factors, given the high level of consanguinity of this population. Further studies are needed to quantify the incidence of the celiac condition in apparently ‘celiac-free' areas such as Sub-Saharan Africa and the Far East. In many developing countries, the frequency of CD is likely to increase in the near future given the diffuse tendency to adopt Western, gluten-rich dietary patterns. As most cases currently escape diagnosis all over the world, an effort should be made to increase the awareness of CD polymorphism. A cost-effective case-finding policy and new strategies of mass CD screening could significantly reduce the morbidity and mortality associated with untreated disease. The current high prevalence of CD is just the last link in a chain of events started about 10,000 years ago after wheat domestication and diffusion from the Middle East. We hypothesize different mechanisms to explain the so-called evolutionary celiac paradox of co-localization of gluten consumption and HLA CD-predisposing genotypes.

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