HLA-G Polymorphisms of The 3'-UTR Region Are Involved in Susceptibility to Non-Infectious Uveitis

HLA-G is a non-classical HLA class I gene encoding a molecule endowed with immunomodulatory properties, playing important immunosuppressive and tolerogenic roles in immuno-privileged organs. Fluctuations in its expression levels have been correlated with the predisposition to autoinflammatory disorders, notably uveitis, characterized by inflammation of the uvea. In the present work, DNA was obtained from saliva samples of 147 Spanish patients with uveitis, with subsequent analysis focusing on the distribution of polymorphisms within the 3'UTR region of the HLA-G gene (a region known to modulate the expression of the HLA-G molecule).

Analysis techniques employed included PCR-RFLP or DNA sequencing. Comparative analysis was conducted against a control cohort comprising 117 healthy individuals.

The frequency of the UTR-2 haplotype is increased in patients affected with anterior uveitis (OR (95% CI) 2.35 (1.06-5.21); p = 0.036). Additionally, a higher number of patients with posterior uveitis bearing in homozygosis the G allele of the 3142 C/G SNP (OR (95% CI) 2.67 (1.15-6.20); p = 0.023), was observed. Both markers are associated with diminished HLA-G expression.

These findings present the first evidence of the involvement of polymorphisms within the 3'UTR region of the HLA-G gene in susceptibility to uveitis.