title: Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic dermatitis (ATOD2) on human chromosome 1q21.
abstract: Psoriasis (PS) is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and altered differentiation. Atopic dermatitis (ATOD) is a chronic inflammatory, pruritic and eczematous disease frequently associated with respiratory atopy. These diseases are associated with distinct immunologic abnormalities and represent typical examples of complex diseases triggered by both genetic and environmental factors, as demonstrated by independent twin studies. Genome wide linkage studies have mapped susceptibility loci on several chromosomes (PSORS1-9; ATOD1-5). Four of them overlap on chromosomes 1q21, 3q21, 17q25 and 20p although ATOD is quite distinct from PS and these two diseases rarely occur together in the same patient. An association fine-mapping study has been performed to refine PSORS4 and ATOD2 susceptibility loci on chromosome 1q21 analyzing two independently collected cohorts of 128 PS and 120 ATOD trios. Genotype and haplotype analysis of PSORS4 and ATOD2 led us to detect significant p value for haplotypes defined by MIDDLE and ENDAL16 markers in both PS (p = 0.0000036) and ATOD (p = 0.0276), suggesting a strict co-localization within an interval of 42 kb. This genomic interval contains a single gene, LOR, encoding for loricrin. Polymorphic markers mapping in regulatory and coding regions did not show evidence of association in neither of the two diseases. However, expression profiles of LOR in skin biopsies have shown reduced levels in PS and increased levels in ATOD, suggesting the existence of a specific misregulation in LOR mRNA production.
authors.affiliation: Department of Biopathology and Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, Tor Vergata University, Rome, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sinibaldi
authors.forename: Loredana
authors.initials: L
authors.lastname: Chini
authors.forename: Viviana
authors.initials: V
authors.lastname: Moschese
authors.forename: Giorgiana
authors.initials: G
authors.lastname: Marulli
authors.forename: Alessia
authors.initials: A
authors.lastname: Provini
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Mauro
authors.initials: M
authors.lastname: Paradisi
authors.forename: Sergio
authors.initials: S
authors.lastname: Chimenti
authors.forename: Elena
authors.initials: E
authors.lastname: Galli
authors.forename: Ercole
authors.initials: E
authors.lastname: Brunetti
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
mesh_terms: D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011565:Psoriasis / Q000235:genetics*