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(Investigative Ophthalmology and Visual Science. 2007;48:3019-3025.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1485
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Association between Heat Shock Protein 70/Hom Genetic Polymorphisms and Uveitis in Patients with Sarcoidosis

Paolo Spagnolo,1,2 Hiroe Sato,1,2 Sara E. Marshall,3 Katerina M. Antoniou,1 Tariq Ahmad,4 Athol U. Wells,1 Muhammad A. Ahad,5 Susan Lightman,5 Roland M. du Bois,1 and Kenneth I. Welsh1

1From the Clinical Genomic Group, National Heart and Lung Institute, Department of Occupational and Environmental Medicine, and the 3Department of Immunology, Imperial College, London, United Kingdom; the 4Gastroenterology Unit, Radcliffe Infirmary, University of Oxford, Oxford, United Kingdom; and the 5Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye Hospital, London, United Kingdom.

PURPOSE. The predisposition to sarcoidosis, a systemic granulomatous disorder of unknown etiology, is genetically determined, and genetics appears also to drive the disease down distinct phenotypic pathways. This study was undertaken to test the hypothesis that sarcoidosis-related uveitis represents a genetically distinct disease subset, by investigating single nucleotide polymorphisms (SNPs) in the HSP-70/1 and HSP-70/Hom genes. HSP70 molecules play a key role in the immune response by functioning both as chaperones and as inducers of proinflammatory cytokine secretion.

METHODS. By sequence-specific primers–polymerase chain reaction (SSP-PCR) five SNPs were evaluated in 270 white patients with sarcoidosis, including 88 with sarcoid-related uveitis, and in 347 matched control subjects. One hundred twenty-five patients with idiopathic anterior uveitis (IAU) and 56 with idiopathic intermediate uveitis (IIU) were also included in the study as disease control subjects.

RESULTS. The HSP-70/Hom rs2075800 G allele frequency was higher in the sarcoid-uveitis group than in both the sarcoid-non-uveitis and control groups (83% vs. 71%, OR = 2.00, Pc = 0.01; and 83% vs. 66%, OR = 2.45, Pc = 0.00005, respectively). Similar results were observed when considering the carriage frequency of the associated haplotype (HSP-70 haplotype 2) across the three study groups (47% vs. 29%, OR = 2.17, Pc = 0.03; and 47% vs. 21%, OR = 3.26, Pc = 0.0003, respectively). In addition, the carriage frequency of the HSP-70 haplotype 2 discriminated among sarcoid-related uveitis, IAU, and IIU (47% vs. 19%, OR = 3.26, Pc = 0.001; and 47% vs. 23%, OR = 2.81, Pc = 0.04, respectively).

CONCLUSIONS. A strong association was found between HSP-70/Hom rs2075800 G and uveitis in patients with sarcoidosis. Further studies are needed to understand the molecular mechanisms underlying this association.






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