A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes.

Autor: Magitta NF; Centre of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway., Bøe Wolff AS, Johansson S, Skinningsrud B, Lie BA, Myhr KM, Undlien DE, Joner G, Njølstad PR, Kvien TK, Førre Ø, Knappskog PM, Husebye ES
Jazyk: angličtina
Zdroj: Genes and immunity [Genes Immun] 2009 Mar; Vol. 10 (2), pp. 120-4. Date of Electronic Publication: 2008 Oct 23.
DOI: 10.1038/gene.2008.85
Abstrakt: Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spectrum of autoimmune diseases. Investigating large patient cohorts from six different autoimmune diseases, that is autoimmune Addison's disease (n=333), type 1 diabetes (n=1086), multiple sclerosis (n=502), rheumatoid arthritis (n=945), systemic lupus erythematosus (n=156) and juvenile idiopathic arthritis (n=505), against 3273 healthy controls, we analyzed four single nucleotide polymorphisms (SNPs) in NALP1. The major allele of the coding SNP rs12150220 revealed significant association with autoimmune Addison's disease compared with controls (OR=1.25, 95% CI: 1.06-1.49, P=0.007), and with type 1 diabetes (OR=1.15, 95% CI: 1.04-1.27, P=0.005). Trends toward the same associations were seen in rheumatoid arthritis, systemic lupus erythematosus and, although less obvious, multiple sclerosis. Patients with juvenile idiopathic arthritis did not show association with NALP1 gene variants. The results indicate that NALP1 and the innate immune system may be implicated in the pathogenesis of many autoimmune disorders, particularly organ-specific autoimmune diseases.
Databáze: MEDLINE