1. J Immunol. 2008 May 15;180(10):6751-9.
Common genetic determinants of uveitis shared with other autoimmune disorders.
Mattapallil MJ(1), Sahin A, Silver PB, Sun SH, Chan CC, Remmers EF, Hejtmancik
JF, Caspi RR.
Author information:
(1)Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892,
USA. mattapallilm@nei.nih.gov
Uveitis is a complex multifactorial autoimmune disease of the eye characterized
by inflammation of the uvea and retina, degeneration of the retina, and blindness
in genetically predisposed patients. Using the rat model of experimental
autoimmune uveitis (EAU), we previously identified three quantitative trait loci
(QTL) associated with EAU on rat chromosomes 4, 12, and 10 (Eau1, Eau2, and
Eau3). The primary goal of the current study is to delineate additional non-MHC
chromosomal regions that control susceptibility to EAU, and to identify any QTLs
that overlap with the QTLs of other autoimmune diseases. Using a set of
informative microsatellite markers and F(2) generations of resistant and
susceptible MHC class II-matched rat strains (F344 and LEW), we have identified
several new significant or suggestive QTLs on rat chromosomes 2, 3, 7, 10, and 19
that control susceptibility to EAU. A protective allele was identified in the
susceptible LEW strain in the Eau5 locus at D7Wox18, and epistatic interactions
between QTLs were found to influence the severity of disease. The newly
identified regions (Eau4 through Eau9) colocalize with the genetic determinants
of other autoimmune disease models, and to disease-regulating syntenic regions
identified in autoimmune patients on human chromosomes 4q21-31, 5q31-33,
16q22-24, 17p11-q12, 20q11-13, and 22q12-13. Our results suggest that uveitis
shares some of the pathogenic mechanisms associated with other autoimmune
diseases, and lends support to the "common gene, common pathway" hypothesis for
autoimmune disorders.
PMCID: PMC2493541
PMID: 18453595 [PubMed - indexed for MEDLINE]
PUBMED: 18453595
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