Optineurin Gene Evaluation in Primary Open Angle Glaucoma Brazilian Patients

Abstract

Purpose:: Glaucoma is a group of eye disorders characterized by progressive degeneration of the optic nerve, leading to correspondent visual loss and is considered the second cause of blindness worldwide. Primary open angle glaucoma (POAG) is a complex disease and its molecular basis is attributed to the interaction of multiple genes and environmental factors. Optineurin (OPTN), located at GLC1E locus is the second gene whose mutations have been associated with POAG. The goal of this study was to investigate the most common alterations reported in this gene, related to the pathogenesis of the disease, in a population of POAG Brazilian patients. There is no report involving the study of the OPTN gene in our population, which is characterized by great ethnic variation.

Methods:: Ninety nine unrelated patients with POAG and 108 unrelated control subjects from UNICAMP and Santa Casa de São Paulo were involved in this study. Five previously reported changes were evaluated through PCR and direct sequencing or RFLP: T34T, E50K, M98K, premature stop (691_692insAG) and R545Q.

Results:: The E50K as well as premature stop (691_692insAG) mutations were not observed either in GPAA patients or in the control group. The M98K mutation was presented in a low percentage in our population, equally distributed: 1 in 99 POAG and 2 in 108 controls. The T34T polymorphism was significantly associated to the development of the disease, when genotypic frequency [POAG X Controls: GG: 62.6% X 77.8%, GA: 28.3% X 15.7% and AA: 9.1% X 6.5% (p=0,05)] and allelic frequency [POAG X Controls: G: 76.8% X 86.6% and A: 23.2% X 13.4% (p<0,05)] were evaluated. The R545Q, a disease-causing mutation in other populations, was present in a higher frequency in our control group than in the POAG patients: 10 in 99 (10.1%) POAG and 23 in 108 (21.3%) controls.

Conclusions:: The Brazilian population has a different spectrum of the most common OPTN mutations. These results suggest that the R545Q alteration is not a disease-causing mutation in our population and also a possible association between the T34T polymorphism and POAG in Brazilian patients.

Keywords: genetics • mutations • intraocular pressure