genetic variants and sarcoidosis-associated uveitis.

PURPOSE

Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood.We determine if variants in confer an increased risk of developing uveitis in adults with sarcoidosis.

METHODS

In this genetic case-control study, 51 total subjects were enrolled: 39 patients diagnosed with sarcoid-related uveitis and 12 patients with systemic sarcoidosis without ocular involvement as controls. Sanger sequencing of the eleven exons of the gene was performed on DNA obtained from whole blood. Sanger sequencing data were aligned against the NCBI-RefSeq reference sequence to identify novel mutations in uveitis patients. For common variants, allele frequencies in cases versus controls were compared using the chi-square test.

RESULTS

There were no significant differences in common variant allele frequencies between sarcoidosis patients with and without uveitis, and none of the pathogenic mutations associated with Blau syndrome were found in this cohort. However, four rare, non-synonymous variants were identified in four patients with ocular sarcoidosis and none of the controls. Variants rs149071116, rs35285618, and 16:g.50745164T > C have never been previously reported to be associated with any disease and may be pathogenic. The fourth variant, rs2066845, is associated with Crohn's disease and psoriatic arthritis.

CONCLUSIONS

Despite the phenotypic overlap between sarcoidosis and Blau syndrome, none of the established pathogenic variants were present in adults with sarcoidosis. However, four novel, rare, non-synonymous variants were identified in four cases with ocular sarcoidosis. Further investigation is needed to explore the potential clinical significance of these polymorphisms.