Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene

Pointon, J. J., Harvey, D., Karaderi, T., Appleton, L. H., Farrar, C., Stone, M. A., Sturrock, R. D., Brown, M. A., & Wordsworth, B. P. (2010) Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene. Genes and Immunity, 11(6), pp. 490-496.

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Ankylosing spondylitis (AS) is polygenic with contributions from the immunologically relevant genes HLA-B27, ERAP1 and IL23R. A recent genome-wide association screen (GWAS) identified associations (P0.005) with the non-synonymous single-nucleotide polymorphisms (nsSNPs), rs4077515 and rs3812571, in caspase recruitment domain-containing protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) on chromosome 9q that had previously been linked to AS. We replicated these associations in a study of 730 AS patients compared with 2879 historic disease controls (rs4077515 P0.0004, odds ratio (OR)1.2, 95% confidence interval (CI)1.1-1.4; rs3812571 P0.0003, OR1.2, 95% CI1.1-1.4). Meta-analysis revealed strong associations of both SNPs with AS, rs4077515 P0.000005, OR1.2, 95% CI1.1-1.3 and rs3812571 P0.000006, OR1.2, 95% CI1.1-1.3. We then typed 1604 AS cases and 1020 controls for 13 tagging SNPs; 6 showed at least nominal association, 5 of which were in CARD9. We imputed genotypes for 13 additional SNPs but none was more strongly associated with AS than the tagging SNPs. Finally, interrogation of an mRNA expression database revealed that the SNPs most strongly associated with AS (or in strong linkage disequilibrium) were those most associated with CARD9 expression. CARD9 is a plausible candidate for AS given its central role in the innate immune response.

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32 citations in Web of Science®
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ID Code: 89385
Item Type: Journal Article
Refereed: Yes
Keywords: genetic association, innate immunity, spondyloarthropathy, caspase recruitment domain containing protein 9, messenger RNA, protein derivative, small nuclear RNA activating complex polypeptide 4, unclassified drug, ankylosing spondylitis, article, CARD9 gene, chromosome 9q, controlled study, female, gene linkage disequilibrium, gene replication, genetic variability, genotype, human, major clinical study, male, priority journal, protein expression, single nucleotide polymorphism, CARD Signaling Adaptor Proteins, Case-Control Studies, Chromosomes, Human, Pair 9, DNA-Binding Proteins, Gene Frequency, Genetic Association Studies, Humans, Polymorphism, Single Nucleotide, Spondylitis, Ankylosing, Transcription Factors
DOI: 10.1038/gene.2010.17
ISSN: 1466-4879
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 Macmillan Publishers Ltd.
Deposited On: 22 Oct 2015 01:16
Last Modified: 26 Jun 2017 02:01

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