A novel optineurin truncating mutation and three glaucoma-associated missense variants in patients with familial amyotrophic lateral sclerosis in Germany.
BACKGROUND Glaucoma is the leading cause of irreversible blindness in the world. Recent evidence indicates genetic susceptibility plays a role in primary open-angle glaucoma (POAG). The authors systematically investigated the association between optineurin (OPTN) gene polymorphisms and POAG. MATERIAL/METHODS A meta-analysis of 25 published genetic association case-control studies, which examined the relation between POAG and the M98K, T34T, and R545Q polymorphisms of the OPTN gene, was carried out. RESULTS For the T34T polymorphism, overall, the heterogeneity between studies was significant (P=0.0009), and the allele A was not associated with the risk of POAG relative to allele G (odds ratio: 1.14 [95% CI, 0.93 to 1.40]). In Asians and adults, the dominant model for allele A produced significant results (odds ratios: 1.50 [1.23 to 1.82] and 1.45 [1.10 to 1.91], respectively). Asian subjects also showed significance under the allele contrast model; however, the recessive model produced no significant results. Regarding the M98K and R545Q polymorphisms, the overall analysis did not detect a statistically significant association (odds ratios for the allele contrast models: 1.16 [0.96 to 1.40] and 1.14 [0.93 to 1.40], respectively). CONCLUSIONS There is evidence of a modest positive association only between T34T polymorphism and POAG in Asians and adults. The M98K and R545Q polymorphisms have no association with POAG susceptibility. However, this meta-analysis exploring combinations of the polymorphisms may help us better understand the genetics of POAG.