Is the GSTM1 null polymorphism a risk factor in primary open angle glaucoma?

PURPOSE: To investigate the association of glutathione S-transferase (GST) GSTM1, GSTT1, and GSTP1 genes with the risk of primary open angle glaucoma (POAG) and clinical features of the disease. METHODS: We conducted a case-control study that included 87 Brazilian patients with POAG and 85 healthy controls matched for age, ethnicity, and sex, whose blood samples were genotyped for polymorphisms in GST genes using polymerase chain reaction (PCR) based methods. RESULTS: The GSTM1 null polymorphism was significantly more common in the POAG than in the controls group (OR: 2.1, 95% CI: 1.13-3.9; p=0.018). The combined GSTM1 null/GSTT1+ genotype and GSTM1 null/GSTP1 Ile/Val or Val/Val was more prevalent in POAG patients, being a risk factor for POAG (OR: 2.4, 95% CI: 1.16-4.9; p=0.016 and OR: 2.7, 95% CI: 1.07-6.74; p=0.033, respectively). The GSTM1 null/GSTT1+ genotype were associated with higher levels of IOP of both eyes and with more severe defect of the right eye optic nerve. The GSTM1 null/GSTP1 Ile/Val or Val/Val genotypes were associated with higher levels of IOP and more advanced defect of the right eye optic nerve and visual field. CONCLUSIONS: We demonstrate that GSTM1 null polymorphism is associated with POAG in the Brazilian population.

Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population.

The present study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with primary open angle glaucoma (POAG). We conducted a case-control study that included 90 patients with POAG and 127 healthy controls whose blood samples were genotyped for the functional polymorphisms T-786C and Glu298Asp of the eNOS gene by Taqman fluorescent allelic discrimination assay. The T-786C polymorphism was significantly associated as a risk factor for POAG among women (OR: 2.28; 95% CI: 1.11 to 4.70, p=0.024) and marginally associated to the risk of POAG in the patients ≥52 years of age at diagnosis (OR: 2.11; 95% CI: 0.98 to 4.55, p=0,055). However, these results was not confirmed after adjustments for gender, age, self-declared skin color, tobacco smoking and eNOS genotypes by multivariate logistic regression model (OR: 2.08; 95% CI: 0.87 to 5.01, p=0.101 and OR: 2.20; 95% CI: 0.95 to 5.12, p=0.067, respectively). The haplotype CG of T-786C and Glu298Asp showed a borderline association with risk of POAG in the overall analysis (OR: 1.76; 95% CI: 0.98 to 3.14, p=0.055) and among women (OR: 2.02; 95% CI: 0.98 to 4.16, p=0.052). Furthermore, the CG haplotype was significantly associated with the development of POAG for the age at diagnosis group ≥52 years (OR: 3.48; 95% CI: 1.54 to 7.84, p=0.002).We suggested that haplotypes of the polymorphisms T-786C and Glu298Asp of eNOS may interact with gender and age in modulating the risk of POAG.