Optineurin (OPTN) Plays a Minor Role in Primary Open–Angle Glaucoma (POAG)

Abstract

Abstract: : Purpose: To determine the role of OPTN in POAG with elevated intraocular pressure (IOP). Methods: 271 primary open–angle glaucoma probands with IOP > 22 mmHg were screened for OPTN mutations. A set of 206 controls belonging to different races including Africans, Caucasians, Hispanics and Asians was analyzed. Genomic DNA from the participants was isolated from the peripheral blood. Coding exons of the OPTN gene were amplified using PCR. Purified PCR products were sequenced using ABI technology. Results: We found causative mutations in four probands: one with an E50K, one with an insAG 691_692, and two with R545Q mutations. In addition, we found 34 POAG affected individuals with the risk–associated alteration, M98K. This change was also found in 23 normal controls. Among subjects of African ancestry 17/70 POAG cases had M98K change (24.3%) compared to 17/54 controls (31.5%). Among Caucasians, 13/185 POAG cases had M98K variation (8.1%) compared to 7/104 controls (6.7%). Conclusions: In screening a set of subjects with POAG with elevated IOP, causative OPTN mutations were found in 4/271 (1.47%). M98K alteration was found in 34/271 POAG cases (12.54 %). This change was also found in 26/206 normal controls (12.62%). M98K seems to be more prevalent in people with African ancestry. Mutations in OPTN may play a minor role in POAG with high IOP. Additionally some interesting observations with regard to the OPTN gene screening in a POAG family that has a mutation in the MYOC gene will be presented.

Keywords: genetics • mutations • gene screening