title: Co-localization of gluten consumption and HLA-DQ2 and -DQ8 genotypes, a clue to the history of celiac disease.
abstract: Celiac disease is an immune-mediated disorder triggered by gluten in genetically susceptible persons. Despite its detrimental effects on human health, it has not disappeared over time. The current evolutionary theory is that celiac disease is more common in areas reached later by agricultural revolution than in countries that started consumption of wheat earlier, due to negative selection caused by celiac disease. We reviewed data on worldwide prevalence of celiac disease, wheat consumption, and frequencies of HLA-celiac-disease-predisposing-genotypes to investigate their mutual relationship. Studies assessing prevalence of celiac disease were identified through a MEDLINE search. Wheat consumption and frequencies of HLA-DQ2-DQ8 were obtained from Food and Agriculture Organization of the United Nations and allelefrequencies.net database. Correlations between celiac disease, wheat consumption, and HLA were analyzed by linear regression. We observed a significant correlation between wheat consumption and HLA DQ2 (p=0.01) and the sum of DQ2 and DQ8 (p=0.01) frequencies. Wheat consumption and HLA-DQ2 tend to co-localize in different continents. The correlation between the prevalence of celiac disease and either DQ2 and/or DQ8, or the product of DQ2+DQ8*wheat consumption was not statistically significant. Co-localization of gluten consumption and HLA-celiac-disease-predisposing-genotypes can be explained by positive selection of HLA-DQ2 genes in wheat-consuming areas, and "demic diffusion" of Middle East farmers into Europe.
authors.affiliation: Department of Pediatrics, University of Catania, Catania, Italy. Electronic address: elenalionetti@inwind.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Lionetti
authors.affiliation: Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Division of Pediatric Gastroenterology and Nutrition and Center for Celiac Research, Massachusetts General Hospital for Children, and Celiac Program - Harvard Medical School, Boston, MA, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Catassi
mesh_terms: D000293:Adolescent; D000328:Adult; D005075:Biological Evolution; D002446:Celiac Disease / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004032:Diet / Q000706:statistics & numerical data*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014943:Global Health; D005983:Glutens; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D016014:Linear Models; D015995:Prevalence; D014908:Triticum; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D005983:Glutens
keywords: Celiac disease; Evolution; HLA; Wheat