The genetics of psoriasis: a complex disorder of the skin and immune system |
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Authors: | Bhalerao, J Bowcock, AM |
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Affiliation: | Department of Internal Medicine, Pediatrics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-8591, USA. |
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Abstract: | In the last few years, molecular genetics analyses have permitted novelinsights into psoriasis, a disease characterized by uncontrolledproliferation of keratinocytes and recruitment of T cells into the skin.The disease affects approximately 1-2% of the Caucasian population and canoccur in association with other inflammatory diseases such as Crohn'sdisease and in association with human immunodeficiency virus (HIV)infection. Given that psoriasis has characteristics of an autoimmunedisease, it is not surprising that HLA studies revealed an association withcertain alleles, notably HLA-Cw6. Despite this HLA component, psoriasis insome families is inherited as an autosomal dominant trait with highpenetrance. Loci at chromosome 17q25 and 4q have been identified followinggenome-wide linkage scans of large, multiply affected families. In the caseof at least the susceptibility locus at 17q25, the development of psoriasisdoes not require the presence of HLA-Cw6. Sib-pair analyses have confirmedthe association with HLA-Cw6, confirmed the existence of a locus at 17q25and identified other possible susceptibility loci. Two independent groupshave reported a third region on chromosome 20p. Despite these findings, theextent of genetic heterogeneity and the role of environmental triggers andmodifier genes is still not clear. The precise role of HLA also still needsto be defined. The isolation of novel susceptibility genes will provideinsights into the precise biochemical pathways that control this disease.Such pathways will also reveal additional candidate genes that can betested for molecular alterations resulting in disease susceptibility. |
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