ABSTRACT
Alopecia areata is a common chronic inflammatory disorder characterized by Tcell infiltration of hair follicles and nails. The inheritance pattern is in keeping with a polygenic inheritance model, and to date, three genetic susceptibility/ severity factors have been identified by means of a candidate gene approach. The HLA DQB and DR alleles on chromosome 6p21.3 have been demonstrated to confer a high risk of disease by both case-control and family-based studies. Interleukin-1 cluster genes, mainly the interleukin-1 receptor antagonist on chromosome 2q12.21, show a strong association with disease severity in alopecia areata and several other autoimmune and inflammatory diseases. Our finding of association of alopecia areata with MXI on chromosome 21q22.3 may explain the increase of alopecia areata in Down’s syndrome. Taken together with the high frequency of alopecia areata in the’ autoimmune polyglandular syndrome type I, the autoimmune regulator (AIRE) gene on chromosome 21q22.3 is a strong candidate gene in alopecia areata. Environmental factors may be involved in initiating disease expression in alopecia areata, but their role remains speculative. Research on pathogenesis has concentrated on the role of the immune system and the nature of the hair follicle pathology, but understanding of the relationship between these remains limited. The new genetic information should help to stimulate research on disease mechanisms and new therapeutic approaches.
