title: Genetic susceptibility and severity of alopecia areata in human and animal models.
abstract: Alopecia areata (AA) is a non-scarring, inflammatory form of hair loss. Human and animal model observations suggest that AA is an autoimmune mediated disease. Genetic influence has been clearly demonstrated in many other autoimmune diseases and one would expect that AA is no exception. AA in rodent models involves genetic susceptibility and it is possible to cross breed the AA phenotype to unrelated rodent strains. Segregation analysis of rodent breeding programs suggests the involvement of several dominant and secondary genes. The increased frequency of AA in genetically related individuals, suggests that human AA expression also involves genetic susceptibility. Within the general population, AA does not segregate as a Mendelian, monogenic trait. AA is a continuous trait with varying degrees of hair loss within the affected population. This suggests that human AA expression involves a complex interaction of multiple genes. AA is most likely a polygenic disease where several, potentially identifiable, major genes affect disease susceptibility and minor severity modifying genes may further affect the phenotype. Here we review the literature on humans and animal models for AA to identify data in support of AA as a polygenic, multivariate penetrance disease with a threshold level for disease onset. Genome wide allelic association screening of animal models and genetically related human sibling pairs may be a suitable approach to identifying susceptibility and severity modifying genes for AA.
authors.affiliation: Department of Dermatology Philipp University, Deutschhausstrasse 9, 35033 Marburg, Germany. kevin@keratin.com
authors.forename: K
authors.initials: K
authors.lastname: McElwee
authors.forename: P
authors.initials: P
authors.lastname: Freyschmidt-Paul
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
authors.forename: R
authors.initials: R
authors.lastname: Happle
authors.forename: R
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000506:Alopecia Areata / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D051379:Mice; D051381:Rats; D012720:Severity of Illness Index
chemical_list: D006680:HLA Antigens