Analysis of OPA1 Gene Polymorphisms in Brazilian Patients With Primary Open Angle Glaucoma

Abstract

Purpose: : Glaucoma has a major genetic basis, whose heterogeneity is illustrated by numerous loci and genes. Autosomal dominant optic atrophy, as well as glaucoma is characterized by progressive optic nerve damage due to degeneration of retinal ganglion cells. Genetic linkage studies identified a dominant optic atrophy gene (OPA1 gene) to chromosome 3q28. Once both conditions share some common characteristics in the optic disc changes, studies have suggested an association between OPA1 gene polymorphisms and primary open–angle glaucoma (POAG). The purpose of this study was to determine the frequency of two polymorphisms in the OPA1 gene (IVS8 +4 e IVS8 +32) in a Brazilian population with POAG.

Methods: : This was a case–control study, evaluating the frequency of the polymorphisms IVS+4 and IVS+32 in the OPA1 gene in patients with POAG and healthy individuals without glaucoma (controls), all of them aged 50 years old or more. The DNA was amplified by PCR and underwent direct sequencing for the identification of the genotypes: position IVS+4: CC, CT, and TT and position IVS+32: TT, TC, and CC.

Results: : 235 individuals (129 POAG patients and 106 controls) were included in the study. Among the POAG patients, the IVS+4 polymorphism showed the genotype CC in 80% and CT in 20 % of the cases, while in the control group, the following distribution was observed: CC in 84%, CT in 13% and TT in 3% of the cases. The distribution of IVS+4 polymorphism genotypes in POAG patients was not significantly different from that observed in control individuals (p=0.07). The same situation was observed with the IVS+32 polymorphism, which showed the following distribution in the POAG and control groups, respectively: TT 16% and 14%; TC 31% and 34%, and CC 53% and 52% (p= 0.845).

Conclusions: : This study was unable to detect an association between IVS+4 and IVS+32 polymorphisms in the OPA1 gene and POAG.

Keywords: genetics • intraocular pressure • ganglion cells