Association of Polymorphic Regulatory Region of TIGR Gene with Glaucoma

PURPOSE: To identify the polymorphism in the regulatory region of trabecular meshwork inducible glucocorticoid response(TIGR) gene and evaluate the association of it with glaucoma. METHODS: 5'regulatory region of TIGR gene of 101 normal persons and 91 unrelated glaucoma patients were analyzed by DNA sequencing and restriction enzyme digestion. To know the possible effects of the polymorphism on the transcription rate of TIGR gene, electrophoretic mobility shift assay and luciferase reporter gene assay were performed with cultured cells, and their extracts of trabecular meshwork and ciliary body in which the gene was expressed. RESULTS: Of the 480 bp examined, G to A transition(G-241A) located at 241 bp upstream from transcription start site was identified and its frequency of occurrence was proved to be higher in steroid induced glaucoma patients(18.9%) compared with that in normal population(8.9%), POAG(8.3%) and normal tension glaucoma patients(6.7%, P<0.05). In mobility shift assay, the G-241A probe was proved to have affinity to some DNA-binding proteins and its affinity was revealed to be two times stronger than that of normal sequence. The luciferase activities, however, were observed to be similar in cells transfected with vectors having normal promoter sequence or G-241A containing one. CONCLUSION: The result suggest that G-241A itself is not a cause of steroid-induced glaucoma but is in linkage disequilibrium with the actual causes of the disease.

Analysis of TIGR Gene Mutation in Glaucoma

In the present study, we have evaluated the mutations of the TIGR[Trabecular meshwork Inducible Glucocorticoid Response] gene, which has been reported to be associated with the glaucoma, in primary open angle glaucoma[POAG], normal tension glaucoma[NTG], and steroid-induced glaucoma[SIG]. We have analyzed the TIGR gene in 18 members of 3 families affected with POAG, 28 familially unrelated patients with POAG, 32 patients with NTG, 30 patients with SIG, and 45 normal subjects.DNA was extracted from the blood samples of each patient, exon 2 and exon 3 of the TIGR gene were amplified by PCR and DNA sequencing was performed.No mutation was found in familially unrelated patients with POAG.Two kinds of mutation[Ser341Pro, Gly367Arg]were found in 3 families affected with POAG.Another mutations, located in exon 3, were detected in one NTG patient and in one SIG patient, but they were silent substitution.Identification of TIGR gene mutation will provide early diagnosis of POAG before irreversible visual impairment develops in cases of positive family history of glaucoma.