Polymorphisms of myocilin and optineurin in primary open angle glaucoma patients

Abstract

To detect the single nucleotide polymorphisms (SNPs) of the myocilin (MYOC) and optineurin (OPTN) genes, and to investigate their associations with high tension glaucoma (HTG) and normal tension glaucoma (NTG). SNPs were detected using polymerase chain reaction (PCR), followed by conformation sensitive gel electrophoresis (CSGE) and fluorescent labeling automated DNA sequencing among 94 unrelated patients with HTG, 48 unrelated patients with NTG, and 77 unrelated control subjects. Fourteen MYOC sequence alterations were identified, five of them: V53A, I304I, T347T, 1-126T > C, and IVS2 + 172C > A, were novel. Among them, V53A was for the first time found in primary open angle glaucoma (POAG) patient. R76K usually occurred with the promoter polymorphism 1-83G > A. No sequence alterations in the MYOC gene showed significant differences among the HTG, NTG and control subjects (all P > 0.05). A total of 12 sequence alterations were identified in the OPTN gene, and three of them: V161M, I407T and L211L, were novel. Among them, I407T and L211L were found only in the HTG patients. The allele and genotype frequencies of T34T in the NTG patients were significantly higher than those of the controls (P = 0.001 and 0.004 respectively). In HTG, only the allele frequency of T34T was 24% (23/96), significantly higher than those of the NTG group (16.5%, 31/188) and the control group (9.1%, 14/154) (both P < 0.05). In addition, IVS8 + 20G > A was found only in the HTG (3.1%, 3/96) and NTG patients (3.7%, 7/188), and had significantly higher frequencies in the HTG and NTG patients when compared with the controls (P = 0.016 and 0.014, and P = 0.027 and 0.026). Polymorphisms in the MYOC and OPTN genes are associated with POAG in Chinese people. Moreover, sequence alterations not causing amino acid changes may play a role in the pathogenesis of POAG.