Polymorphisms Of Myocilin And Optineurin In Primary Open Angle Glaucoma Patients

Glaucoma is a progressive optic neuropathy characterized by a particular pattern of visual field loss and optic nerve head damage. It is the second leading cause of blindness in the world, affecting approximately 67 million people, of which 6.7 million are bilaterally blind. Primary Open Angle Glaucoma (POAG) is one of the common types of glaucoma. It has been reported that the genetic factors are involved in the pathogenesis of POAG, and perhaps play the central role. According to the intraocular pressure (IOP), POAG can be grouped into high tension glaucoma (HTG) and normal tension glaucoma (NTG). Myocilin (MYOC) and Optineurin (OPTN) are the two disease associated genes which has been found to link with POAG. And recently, WDR36 which located in the seventh chromosome loci GLC1G was also identified as the third POAG associated gene.Chinese is one of the largest ethnic groups in the world, while the mutation screening in this population is very rare. In order to detect the single nucleotide polymorphisms (SNP) of the MYOC and OPTN genes, and to investigate their associations with HTG and NTG in Taiwan Chinese population, we recruited 94 unrelated patients with HTG, 48 unrelated patients with NTG and 77 unrelated control subjects. We use polymerase chain reaction (PCR), followed by conformation sensitive gel electrophoresis (CSGE) and fluorescent labeling automated DNA sequencing to detect the SNPs in the MYOC and OPTN genes. Fourteen MYOC sequence alterations were identified in our study subjects, five of them were novel, i.e.; V53A, I304I, T347T, 1-126T>C and IVS2+172C>A. Among them, V53A was for the first time found in a primary open angle glaucoma patient. R76K is usually occurred with the promoter polymorphism 1-83G>A. A total of 12 sequence alterations were identified in the OPTN gene, three of them were novel, i.e.; V161M, I407T and L211L, I407T and L211L were found only in HTG Among all the sequence alterations, we identified three disease-causing mutations (DCM), V53A, D208E in MYOC and I407T in OPTN, and the frequencies of MYOC and OPTN mutations in POAG were 1.4% and 0.7% respectively, both were a bit lower than the overall frequency 2-4% of MYOC mutations in the world and 16.7% of OPTN mutations in the...