OPTN gene: Profile of patients with glaucoma from India

[摘要] Purpose: Optineurin gene (OPTN) mutations are reported inprimary open angle glaucoma patients (POAG) from different populations.The coding and noncoding regions of OPTN were screened for mutationsin 100 Indian high tension glaucoma patients (HTG). The frequency of theOPTN M98K mutation in an additional 120 patients (70 HTG and 50normal tension glaucoma [NTG]) was analyzed by restriction enzymedigestion.Methods: The HTG patients (about 40 years of age) were characterizedby open angles on gonioscopy, with raised intraocular pressure (IOP)more than 21 mmHg (<21 mmHg on office diurnal phasing for NTG), andtypical glaucomatous disc changes with corresponding visual fielddefects in the absence of any secondary cause. One hundred HTG patientsand controls were screened for OPTN mutations by direct sequencingusing an ABI prism 310/3100 Avant genetic analyzer. The M98K status wasanalyzed by restriction enzyme digestion with StuI. Agenotype/phenotype correlation was also attempted for OPTN sequencealterations with clinical parameters such as age at diagnosis,intraocular pressure, cup:disc ratio, etc. The putative change in thetranscription factor binding site for the IVS7 +24G>A polymorphismwas attempted with AliBaba software (version 2.1).Results: Six sequence alterations were observed in the 100 POAGpatients by direct sequencing. The M98K substitution was observed in atotal of 10 patients (7/170 HTG and 3/50 NTG) contributing to 4.1% inHTG and 6% in the NTG group and not in the controls. The IVS7+24G>Anucleotide change showed a significant difference in the HTG group(7/100) when compared to the control group (0/100) and found to beassociated with increased IOP at diagnosis (p=0.03). The IVS7+24G>Apolymorphism resulted in the creation of binding sites for transcriptionfactors NF-1 and CPE that were not present in the wild type.Conclusions: The current study suggests a possible role of SNPsrather than mutations in OPTN in POAG pathology in the Indianpopulation.

[学科分类] 生物化学/生物物理