Molecular genetics of psoriasis
Year: 2003
Type: dissertation
Study design: Observational Study
Abstract: Psoriasis is a chronic inflammatory skin disease. Based on family studies, a strong genetic component exists in the etiology of psoriasis, but environmental factors are also needed to trigger the disease onset. Both linkage and association analyses have assigned the major locus for psoriasis susceptibility, PSORS1, to 6p21.3 in all populations studied. The PSORS1 locus has been narrowed down to an approximately 200 kb region in the centromeric part of the MHC class I region. In this study, a novel candidate gene at the PSORS1 locus, HCR (Pg8), was cloned and found to be highly polymorphic. In a large trio family material from seven different populations, a specific allele of the HCR gene, HCR*WWCC, was shown to be strongly associated with chronic plaque psoriasis (PV). However, two previously identified susceptibility alleles of the locus, HLA-Cw*6 and CDSN*5, showed a similar association. These three susceptibility alleles were found to belong to the same extended susceptibility haplotype and their separation was not possible even with a sample size of almost 1700 chromosomes. The three PSORS1 susceptibility alleles were also studied in two clinical variants of psoriasis, guttate psoriasis (GP) and palmoplantar pustulosis (PPP), to see whether the locus was involved in the pathogenesis of subtypes and whether these could be used to differentiate the three alleles. GP was shown to have a similar but even stronger association with PSORS1 susceptibility alleles than PV, however, it did not help in separating the three genes. PPP was not associated with any of the PSORS1 alleles, suggesting a different etiology or molecular mechanism than for PV or GP. Functional evidence for HCR as a potential psoriasis gene was also gained. Expression of the HCR mRNA Kari Asumalahti defended her thesis on April 3, 2003 in Helsinki Medical Faculty. Faculty Opponent was James T. Elder, MD, PhD, Professor of Dermatology, Department of Dermatology, University of Michigan, Michigan, USA and Supervisor has been Professor, Juha Kere, MD, PhD, Department of Biosciences at Novum and Clinical Research Center, Karolinska Institute, Sweden and Department of Medical Genetics, University of Helsinki
Source: Työväentutkimus Vuosikirja
Author: Kati Asumalahti
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1919890994