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NALP1 in vitiligo-associated multiple autoimmune disease.

Jin, Y; Mailloux, CM; Gowan, K; Riccardi, SL; LaBerge, G; Bennett, DC; Fain, PR; Spritz, RA (2007) NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med, 356 (12). pp. 1216-1225. ISSN 1533-4406 https://doi.org/10.1056/NEJMoa061592
SGUL Authors: Bennett, Dorothy Catherine

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Abstract

BACKGROUND: Autoimmune and autoinflammatory diseases involve interactions between genetic risk factors and environmental triggers. We searched for a gene on chromosome 17p13 that contributes to a group of epidemiologically associated autoimmune and autoinflammatory diseases. The group includes various combinations of generalized vitiligo, autoimmune thyroid disease, latent autoimmune diabetes in adults, rheumatoid arthritis, psoriasis, pernicious anemia, systemic lupus erythematosus, and Addison's disease. METHODS: We tested 177 single-nucleotide polymorphisms (SNPs) spanning the 17p13 linkage peak for association with disease and identified a strong candidate gene. We then sequenced DNA in and around the gene to identify additional SNPs. We carried out a second round of tests of association using some of these additional SNPs, thus elucidating the association with disease in the gene and its extended promoter region in fine detail. RESULTS: Association analyses resulted in our identifying as a candidate gene NALP1, which encodes NACHT leucine-rich-repeat protein 1, a regulator of the innate immune system. Fine-scale association mapping with the use of DNA from affected families and additional SNPs in and around NALP1 showed an association of specific variants with vitiligo alone, with an extended autoimmune and autoinflammatory disease phenotype, or with both. Conditional logistic-regression analysis of NALP1 SNPs indicated that at least two variants contribute independently to the risk of disease. CONCLUSIONS: DNA sequence variants in the NALP1 region are associated with the risk of several epidemiologically associated autoimmune and autoinflammatory diseases, implicating the innate immune system in the pathogenesis of these disorders.

Item Type: Article
Additional Information: From New England Journal of Medicine, Jin, Y; Mailloux, CM; Gowan, K; Riccardi, SL; LaBerge, G; Bennett, DC; Fain, PR; Spritz, RA, NALP1 in Vitiligo-Associated Multiple Autoimmune Disease, 356, 1216-1225 Copyright © 2007 Massachusetts Medical Society. Reprinted with permission.
Keywords: Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Apoptosis Regulatory Proteins, Autoimmune Diseases, Chromosomes, Human, Pair 17, Genetic Linkage, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Inheritance Patterns, Logistic Models, Molecular Sequence Data, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Sequence Alignment, Sequence Analysis, DNA, Vitiligo, Chromosomes, Human, Pair 17, Humans, Vitiligo, Autoimmune Diseases, Genetic Predisposition to Disease, Adaptor Proteins, Signal Transducing, Logistic Models, Sequence Alignment, Sequence Analysis, DNA, Amino Acid Sequence, Genotype, Inheritance Patterns, Polymorphism, Single Nucleotide, Molecular Sequence Data, Apoptosis Regulatory Proteins, Promoter Regions, Genetic, Genetic Variation, Genetic Linkage, Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, MEDICINE, GENERAL & INTERNAL, COLD AUTOINFLAMMATORY SYNDROME, SUSCEPTIBILITY LOCI, CROHNS-DISEASE, UNITED-STATES, GENE, EPIDEMIOLOGY, MUTATIONS, APOPTOSIS, FAMILY, SYNDROME/, 11 Medical And Health Sciences, General & Internal Medicine
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: N Engl J Med
ISSN: 1533-4406
Language: eng
Dates:
DateEvent
22 March 2007Published
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
AI46374NIAID NIH HHSUNSPECIFIED
AR45584NIAMS NIH HHSUNSPECIFIED
DK57538NIDDK NIH HHSUNSPECIFIED
PubMed ID: 17377159
Web of Science ID: WOS:000245101900006
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111251
Publisher's version: https://doi.org/10.1056/NEJMoa061592

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