Artikel
A genome-wide scan identifies 3 loci for acute anterior uveitis, including one locus unassociated with ankylosing spondylitis
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Veröffentlicht: | 22. September 2004 |
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Gliederung
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Objective
To conduct a genome-wide scan to search for loci associated with acute anterior uveitis.
Methods
Families with 2 or more members who have acute anterior uveitis and/or ankylosing spondylitis (AS) were included. Genomic DNA was extracted from blood cells and PCR-genotyped using the ABI Prism Linkage Map MD-10 system (Applied Biosystems, Foster City, CA). Evidence for linkage was determined by nonparametric multipoint linkage analysis using Gene Hunter Plus. The transmission disequilibrium test was also performed. The genome-wide scan for acute anterior uveitis was compared to one for ankylosing spondylitis performed by the NASC. Where possible, the uveitis phenotype was verified by ophthalmological record review. If no ophthalmology records were available, the assignment of a uveitis phenotype was based on self report AND documentation of uveitis in a non-ophthalmological medical record (usually noted by a rheumatologist). AS was confirmed either by self-report or by radiographic disease determination.
Results
Out of 978 individuals genotyped, 244 were affected with acute anterior uveitis. The data presented represent 76 affected sibling pairs for acute anterior uveitis. Of these, 6 sib pairs denied any symptoms of AS, 12 uveitis sib pairs were discordant for AS and the remaining 58 uveitis sib pairs were concordant for AS. A region on chromosome 9p showed a striking association with uveitis but not AS. The maximum LOD score at this region was 3.69 for uveitis, while the LOD score for the AS cohort was not significant (<1.0). Additional regions with significant linkage include the MHC locus on chromosome 6, and a region at chromosome 1q. However, these regions also showed significant linkage with AS. Transmission disequilibrium analyses supported the genome-wide scan linkage findings, including the 9p uveitis association.
Conclusions
This is the first time that a genetic region for acute anterior uveitis has been identified by genome-wide scan. These data reveal a region on chromosome 9p as a predisposing factor in uveitis. Comparison to a companion AS scan indicates that this region is unique to the uveitis phenotype. Fine-mapping and/or candidate gene analyses should reveal the relevant gene(s) on chromosome 9.