Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-04

AUTHORS

S L Musone, K E Taylor, J Nititham, C Chu, A Poon, W Liao, E T Lam, A Ma, P-Y Kwok, L A Criswell

ABSTRACT

The TNFAIP3 locus at 6q23, encoding A20, has been associated with multiple autoimmune diseases (AIDs). In this study, we sequence the coding portions of the gene to identify contributing causal polymorphisms that may explain some of the observed associations. A collection of 123 individuals from the Multiple Autoimmune Disease Genetics Consortium (MADGC) collection, each with multiple AIDs (mean=2.2 confirmed diagnoses), and 397 unrelated healthy controls were used for initial sequencing. A total of 32 polymorphisms were identified in the sequencing experiments, including 16 novel and 11 coding variants. Association testing in the entire MADGC collection (1,008 Caucasians with one or more AIDs and 770 unaffected family controls) revealed association of a novel intronic insertion-deletion polymorphism with rheumatoid arthritis (RA) (odds ratio (OR)=2.48, P=0.041). Genotyping of the most common coding polymorphism, rs2230926, in the MADGC collection and additional control individuals revealed a significant association with Sjögren's syndrome (OR=3.38, P=0.038), Crohn's disease (OR=2.25, P=0.041), psoriasis (OR=0.037, P=0.036) and RA (OR=1.9, P=0.025). Finally, haplotype and additional testing of polymorphisms revealed that cases were enriched for 5' and 3' untranslated region variants (one-sided P-value=0.04), but not specifically for common (>2% minor allele frequency), rare, exonic, intronic, non-synonymous or synonymous variants. More... »

PAGES

176

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/gene.2010.64

    DOI

    http://dx.doi.org/10.1038/gene.2010.64

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1025188726

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21326317


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