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Characterization of the loricrin ( LOR ) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus
Author(s) -
Giardina E.,
Capon F.,
De Rosa MC.,
Mango R.,
Zambruno G.,
Orecchia A.,
Chimenti S.,
Giardina B.,
Novelli G.
Publication year - 2004
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1529-8817.2004.00118.x
Subject(s) - genetics , locus (genetics) , biology , candidate gene , linkage disequilibrium , genetic linkage , loricrin , gene , psoriasis , gene mapping , haplotype , allele , chromosome , immunology , cellular differentiation , involucrin
Summary Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Non‐parametric linkage analyses have mapped many susceptibility loci on different chromosomes. We mapped one of these loci, PSORS4 , on human chromosome 1q21. Using the linkage disequilibrium approach, we refined the critical region to a specific genomic interval of about 100 Kb which contains only the loricrin ( LOR ) gene. Here we report a genetic and functional study of this gene to verify its involvement in psoriasis pathogenesis. We document low expression of LOR in psoriatic skin of patients selected from families in which the disease was segregrating with the PSORS4 locus. Re‐sequencing of the entire gene in a subset of patients revealed the existence of novel polymorphisms able to influence the protein structure, as shown by molecular modelling studies. However, no evidence for genetic association was detected in a large cohort of Italian nuclear families. This rules out the LOR gene as a candidate for the PSORS4 locus.