SQSTM1 GENE, AUTOPHAGY, AND GLAUCOMA

Abstract

Purpose : Mutations in two autophagy genes, TBK1 and OPTN, have been associated with normal tension glaucoma. TBK1 encodes a kinase that phosphorylates OPTN, an autophagy receptor. TBK1 also phosphorylates another autophagy receptor, sequestosome 1 (SQSTM1 or p62). Consequently, we hypothesize that mutations in SQSTM1 are also associated with normal tension glaucoma.

Methods : A cohort of 331 normal tension glaucoma patients and 157 ethnically-matched controls from Iowa were tested for mutations in the SQSTM1 gene using bi-directional Sanger sequencing of amplimers spanning all 24 exons. The frequency of non-synonymous variations detected in SQSTM1 was compared between cases and controls using Fisher’s exact test.

Results : DNA sequencing of SQSTM1 has been completed on more than 95% of the gene. A total of 22 different variations were detected including 12 non-synonymous and 10 synonymous variations. When the frequency of the non-synonymous variations was compared between the cohort of normal tension glaucoma patients and the cohort of controls, no significant difference was detected (p = 0.24).

Conclusions : Autophagy has been implicated in the pathophysiology of normal tension glaucoma by prior genetic studies of TBK1 and OPTN. These studies suggest that mutations in additional autophagy genes might also be involved in glaucoma pathogenesis. Mutations in SQSTM1, however, do not appear to be a common cause of normal tension glaucoma.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.