Association and linkage of human leukocyte antigens with psoriasis - Revisited

Abstract

Until recently blood group and HLA antigens have been used extensively to study associations with human disease. Case control studies reproducibly showed significant associations of particular HLA antigens with various human diseases. These were mainly autoimmune diseases such as juvenile diabetes, multiple sklerosis, rheumatoid arthritis, psoriasis and celiac disease, but also others, e.g. narcolepsy and familial hemochromatosis. With restriction fragment length polymorphism (RFLP), short tandem repeats (STR) and recently single nucleotide polymorphism of DNA, many polymorphic markers spread across the entire genome have been available for about 10 years. These markers were successfully applied in family-based linkage studies to localize disease genes. Today we recognize that successful positional cloning with linkage analysis is mainly limited to rare diseases with Mendelian trait. But for most of the common familial diseases (e.g. juvenile diabetes and psoriasis) a simple Mendelian trait seems unlikely. A polygenic model is more appropriate. This complicates the search and definition of susceptibility genes. In addition within the HLA gene region linkage studies are hampered by allelic association between neighboring genes (linkage disequilibrium), effecting disease associations. Case control studies in different ethnic populations may be a solution to this problem.