gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

A genome-wide scan identifies 3 loci for acute anterior uveitis, including one locus unassociated with ankylosing spondylitis

Meeting Abstract

  • corresponding author F. Mackensen - Interdisziplinäres Uveitiszentrum, Universitäts-Augenklinik Heidelberg
  • M.D. Becker - Interdisziplinäres Uveitiszentrum, Universitäts-Augenklinik Heidelberg
  • L. Jin - Center for Genome Information, University of Cincinnati, Cincinnati, USA
  • T. Doyle - Casey Eye Institute, Oregon Health & Science University, Portland, USA
  • G. Zhang - Center for Genome Information, University of Cincinnati, Cincinnati, USA
  • J. Luo - Center for Genome Information, University of Cincinnati, Cincinnati, USA
  • J.R. Smith - Casey Eye Institute, Oregon Health & Science University, Portland, USA
  • J.E. Coffman - Casey Eye Institute, Oregon Health & Science University, Portland, USA
  • J.D. Reveille - University of Texas, Houston, USA
  • J.T. Rosenbaum - Casey Eye Institute, Oregon Health & Science University, Portland, USA
  • T.M. Martin - Casey Eye Institute, Oregon Health & Science University, Portland, USA

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogFR.16.06

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dog2004/04dog307.shtml

Veröffentlicht: 22. September 2004

© 2004 Mackensen et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

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.