Genetic factors in pemphigus.
Epidemiological studies performed in different ethnic populations and family studies, notably based on a partial phenotype of the autoimmune process, indicate that genetic factors are involved in the occurrence of pemphigus. However, the precise heritability remains uncertain in the absence of twin concordance rate studies. Among the different strategies available to identify genetic factors participating in autoimmune disease susceptibility, only population studies based on case-control design have been performed in pemphigus. These studies consistently showed that MHC locus, in particular HLA class II alleles, are associated with pemphigus vulgaris and pemphigus foliaceus. Other genes of the MHC locus may also participate in disease susceptibility as shown by studies using microsatellite markers across different regions of the MHC. It is likely that other non-MHC genes are involved in the pathogenesis of pemphigus. In particular, involvement of a polymorphic variant of desmoglein 1 gene was shown to be associated with pemphigus foliaceus and to interact in an epistatic manner with MHC class II genes to contribute to the autoimmune process. Other candidate genes to which a role can be assigned in the disease pathogenesis should be considered to design case-control or family-based association studies. Genome scan studies which require a large number of multiplex families to reach statistical power, should also be considered in the endemic form of pemphigus foliaceus because of the high number of familial cases.
Tron
François
F
Unité INSERM 519 - IFRMP 23, Hôpital Charles Nicolle, Faculté Mixte de Médecine et de Pharmacie, 22, Boulevard Gambetta, 76183 Rouen Cedex, France. francois.tron@chu-rouen.fr
Gilbert
Danièle
D
Mouquet
Hugo
H
Joly
Pascal
P
Drouot
Laurent
L
Makni
Sondès
S
Masmoudi
Hatem
H
Charron
Dominique
D
Zitouni
Mondher
M
Loiseau
Pascale
P
Ben Ayed
Mourad
M
D000483:Alleles; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D010392:Pemphigus / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D040641:Quantitative Trait Loci / Q000235:genetics* / Q000276:immunology
D003598:Cytoskeletal Proteins; C495297:DSG1 protein, human; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II