NALP1 in vitiligo-associated multiple autoimmune disease.
N Engl J Med
; 356(12): 1216-25, 2007 Mar 22.
Article
en En
| MEDLINE
| ID: mdl-17377159
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Vitíligo
/
Cromosomas Humanos Par 17
/
Predisposición Genética a la Enfermedad
/
Proteínas Adaptadoras Transductoras de Señales
/
Proteínas Reguladoras de la Apoptosis
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
N Engl J Med
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos