Analysis of optineurin (OPTN) gene mutations in subjects with and without glaucoma: the Blue Mountains Eye Study

Background: The optineurin (OPTN) gene has been reported to possess both causal as well as risk-associated alleles for open-angle glaucoma. However, these findings have so far only been reported in family and clinic based studies. The aim of this study was to investigate the spectrum of mutations and gene variants in OPTN that might be present in people with glaucoma from a population-based study, the Blue Mountains Eye Study (BMES). Methods: A total of 108 subjects of Caucasian origin were identified at baseline in the BMES as having open-angle glaucoma. Blood samples were available from 27 of these, of whom 18 had high-tension glaucoma and the remaining nine had normal-tension glaucoma. Ninety-four control subjects were chosen at random from the BMES, who satisfied the criteria of not having glaucoma at baseline and were over age 70 years. The 13 coding exons (exons 4-16 inclusive) and their intron-exon boundaries of OPTN were screened by the use of single-strand conformation polymorphism. Samples exhibiting mobility shifts were di-deoxy nucleotide sequenced. The M98K polymorphism was additionally screened using the restriction enzyme StuI in all cases and controls in this study. Results: The M98K risk-associated alteration was identified in 2/18 (11%) subjects with high-tension glaucoma, 0/9 subjects (0%) with normal-tension glaucoma and 3/94 (3.2%) controls. However, association of this variant with disease was not significant (P = 0.2 for each phenotype) for either high-tension glaucoma or normal-tension glaucoma. A novel variant (P556P in exon 16) was found in one subject with open-angle glaucoma and a previously described variant (exon 7) was found in a further subject with open-angle glaucoma and in one control. No other OPTN variants were identified in this study cohort. Conclusions: Cross-sectional analysis from baseline observations of the BMES suggested that the M98K risk-associated allele appeared at a higher prevalence in high-tension glaucoma compared with controls, although this finding was not statistically significant.