Gene variant linked to VKH syndrome

This prospective study found that a protein tyrosine phosphatase non-receptor 22 (PTPN22) gene variant is associated with a higher risk of Vogt-Koyanagi-Harada (VKH) syndrome in the Chinese Han population.

PTPN22 is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to VKH syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis.

Subjects included 1,005 patients with VKH syndrome, 302 patients with ankylosing spondylitis-associated AAU, and 2,010 normal controls–all Chinese Han. Tests included cell isolation and culture, real-time quantitative PCR, cell proliferation assay and cytokine analysis.

The authors found a strong association between a functional variant of the PTPN22 gene--rs2488457--with VKH syndrome but not with ankylosing spondylitis. Individuals carrying the rs2488457 CC genotype showed decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 compared to those carrying the GC genotype. They write that it remains unclear why certain uveitis entities are associated with PTPN22 gene polymorphisms and others are not.

They note that these results confirm earlier findings pointing to PTPN22 as a critical candidate susceptibility gene for immune-related diseases. Most studies on the association between immune disorders and PTPN22 have shown an association with the 1858C/T rs2476601 polymorphism. This polymorphism is absent in Chinese Han, but rs2488457 (-1123G/C) has been shown to be in linkage disequilibrium with rs2476601 and this area of the gene may have functional consequences. Further studies are needed to clarify the exact molecular mechanisms involved.

The lack of an association between PTPN22 polymorphisms and ankylosing spondylitis or ocular Behcet’s disease suggests that the PTPN22 association with uveitis may be confined to those entities that involve an autoimmune pathogenesis. This finding is interesting and deserves further investigation.