Glutathione S-transferase M1 and T1 polymorphisms in Arab glaucoma patients.

PURPOSE: Glutathione S-transferases (GSTs) are a family of enzymes that inactivate xenobiotics and endogenous end products formed as secondary metabolites during oxidative stress. In humans, GSTT1 and GSTM1 deletion genotypes (T0M1, T1M0, and T0M0) are associated with a variety of pathologic processes including certain ophthalmologic diseases. METHODS: We compared the prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by multiplex polymerase chain reaction, in 107 Arab patients with glaucoma (49 with primary open-angle glaucoma, 29 with pseudoexfoliation glaucoma, and 29 with primary angle-closure glaucoma) to 120 age, sex, and ethnically matched controls. RESULTS: All three GST polymorphisms were significantly more common in the entire glaucoma group (p<0.0167) than in controls. However, when patients were stratified by glaucoma type, the deletion genotype, T0M0, was not particularly associated with any type of glaucoma tested. The T1MO genotype was more common among patients with each type of glaucoma than among controls whereas T0M1 genotype was more common among pseudoexfoliation glaucoma (PEG) and primary open-angle glaucoma (POAG) patients than controls. CONCLUSIONS: The overall results indicate a possible variable association between various GSTT1 and GSTM1 genotypes and glaucoma in this population. Decreased GST function might interfere with the metabolism of oxidative intermediates and exacerbate the direct or indirect damaging effects of oxidative stress on the optic nerve. It is possible that these GST polymorphisms may be risk factors for glaucoma.

Nuclear and mitochondrial analysis of patients with primary angle-closure glaucoma.

PURPOSE: Certain types of glaucoma are linked to nuclear genetic mutations or to mitochondrial disturbances. In this study, patients with primary angle-closure glaucoma (PACG) were examined for mutations in nuclear genes reported to be associated with glaucoma and for possible mitochondrial abnormalities. METHODS: In patients with PACG, the nuclear genes MYOC, OPTN, CYP1B1, WDR36, OPA1, and OPA3 were sequenced, the entire mitochondrial (mt)DNA coding region was sequenced, relative mtDNA content was measured, and mitochondrial respiratory activity (MRA) was assessed. RESULTS: No novel or previously reported mutations were present in the nuclear genes MYOC, OPTN, CYP1B1, WDR36, OPA1, and OPA3 in 29 patients with PACG. Four (13.8%) patients had potentially pathologic mtDNA nucleotide changes not found in control subjects. The patients with PACG did not differ significantly from the control subjects in relative mitochondrial content and had only a small decrease in MRA (2.4%) of indeterminate significance. CONCLUSIONS: These Middle Eastern patients with PACG had no mutations in nuclear genes associated with other types of glaucoma or inherited optic neuropathies. Mitochondrial abnormalities were minimal, and the overall pattern of those abnormalities was distinctly different from that of Leber hereditary optic neuropathy, nonarteritic ischemic optic neuropathy, primary open-angle glaucoma, and optic neuritis. These results are consistent with the hypothesis that anatomic factors may be more important determinants for PACG than the genetic and mitochondrial factors evaluated here.