J Korean Ophthalmol Soc.  2001 Mar;42(3):519-526.

Association of Polymorphic Regulatory Region of TIGR Gene with Glaucoma

• Koo HJ
• Son S
• Kee C

Abstract

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.

Keyword

TIGR gene; DNA sequencing; Restriction enzyme digestion; Electrophoretic mobility shift assay; Luciferase reporter gene assay; Steroid induced glaucoma

MeSH Terms

Cells, Cultured
Ciliary Body
Digestion
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Genes, Reporter
Glaucoma*
Humans
Linkage Disequilibrium
Low Tension Glaucoma
Luciferases
Regulatory Sequences, Nucleic Acid*
Sequence Analysis, DNA
Trabecular Meshwork
Transcription Initiation Site
DNA-Binding Proteins
Luciferases