title: NFKBIZ in Psoriasis: Assessing the association with gene polymorphisms and report of a new transcript variant.
abstract: The IκBζ protein (NFKBIZ gene) is a nuclear inhibitor of NF-κB and plays an important role in the pathogenesis of Psoriasis (Psor). We sought to determine whether common NFKBIZ variants were associated with the risk of developing Psor. A total of 392 patients and 336 controls were genotyped for a common intron 10 indel that could affect pre-mRNA splicing. We found a significantly higher frequency of the insertion among the cw6-positive patients (p=0.01). Cw6-positive+intron 10 ins/ins were significantly more frequent in the patients (OR=3.61). The analysis of the cDNA from leukocytes showed a NFKBIZ transcript lacking exon 10, present in all the tested samples. This new alternative transcript lacks a domain predicted to interact with the NFKB1/p50 protein. Functional studies to define the effect of this alternative transcript on the regulation of the NF-κB pathway are necessary.
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain; Dept Medicine, Universidad Oviedo, Oviedo, Spain. Electronic address: pablocotosegura@gmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Coto-Segura
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Gonzalez-Lara
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Eiris
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Batalla
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Gómez
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Sheila
authors.initials: S
authors.lastname: Requena
authors.affiliation: Reumatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Queiro
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Iglesias
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain; Dept Medicine, Universidad Oviedo, Oviedo, Spain. Electronic address: eliecer.coto@sespa.es.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*; D012326:RNA Splicing; D012306:Risk; D015398:Signal Transduction; D013030:Spain
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020672:I-kappa B Proteins; D016328:NF-kappa B; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins
keywords: Gene polymorphism; NF-KB; NFKBIZ; Psoriasis