Optineurin Sequence Variants Do Not Predispose to Primary Open Angle Glaucoma

Abstract

Abstract: : Purpose: To investigate the role of sequence variants in optineurin (OPTN) in primary open-angle glaucoma (POAG). Recent studies have suggested that mutations and polymorphisms in optineurin may cause or increase susceptibility to normotensive glaucoma (Rezai et al., Science 295: 1077). Methods: To assess the influence of optineurin in the more common high-tension POAG, we screened the probands from a set of 86 adult-onset POAG families. Criteria for inclusion include age of onset greater than 35 years, elevated interocular pressure ≥ 22mm Hg in both eyes, optic nerve damage, and corresponding visual field loss in at least one eye. Transgenomic WAVE denaturing high performance liquid chromatography (dHPLC) was used to screen for sequence variants in the optineurin gene. Pools of genomic DNA from 3 individuals were subjected to dHPLC at several different temperatures. Pools displaying altered column retention time were sequenced to confirm and identify sequence variants. Exons 4 and 5, containing the previously reported E50K and M98K variants, were sequenced in their entirety. Results: Within this sample of 86 probands and 80 controls, we detected the M98K variant in 10% of affected individuals, as well as 10% of controls. We did not detect the E50K variant in any of the individuals tested nor did we detect any other polymorphisms within the optineurin coding sequence. However, we did detect six intronic SNPs, none of which are predicted to cause splice defects. Conclusions: This data suggests that variations in the optineurin gene do not cause or predispose individuals to adult onset POAG.

Keywords: genetics • intraocular pressure • trabecular meshwork