title: Initial description of the human NLRP3 promoter.
abstract: Mutations in NLRP3 (CIAS1) are identified in a continuum of related inflammatory disorders, known as cryopyrinopathies since NLRP3 codes for the protein cryopyrin. Approximately 40% of patients with classic presentation lack mutations in the coding region of NLRP3 suggesting heterogeneity or epigenetic factors. Cryopyrin is a key regulator of proinflammatory cytokine release. Therefore, variations in the NLRP3 promoter sequence may have effects on disease state in patients with cryopyrinopathies and other inflammatory diseases. In this report, we confirmed three 5'-untranslated region splice forms with two separate transcriptional start sites, and identified potential promoter regions and six new DNA promoter variants. One variant is unique to a mutation negative cryopyrinopathy patient and increases in vitro gene expression. Additional studies can now be performed to further characterize the NLRP3 promoter and sequence variants, which will lead to better understanding of the regulation of NLRP3 expression and its role in disease.
authors: Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
authors: J P
authors: JP
authors: Anderson
authors: J L
authors: JL
authors: Mueller
authors: A
authors: A
authors: Misaghi
authors: S
authors: S
authors: Anderson
authors: M
authors: M
authors: Sivagnanam
authors: R D
authors: RD
authors: Kolodner
authors: H M
authors: HM
authors: Hoffman
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007962:Leukocytes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011401:Promoter Regions, Genetic / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D022821:RNA Splice Sites