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Allan A. Hunter, III, Paul Spechler, David Telander, Joshua Dunaief; GSTM1 and GSTM5 Polymorphisms in AMD Patients. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2932.
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Age related macular degeneration (AMD) is the leading cause of blindness in the elderly. Evidence suggests oxidative stress plays a role in the disease. We have found recently that mRNA and protein levels of two antioxidant enzymes, GSTM1 and GSTM5, are diminished in post-mortem AMD retinas relative to age-matched controls. Deletion of the GSTM1 gene has also been reported. In this study, we assessed the genomic copy number of GSTM1 and GSTM5 to determine whether deletion could explain our observed reduction in mRNA levels in AMD versus age-matched controls.
Cheek swab DNA samples were collected from 51 AMD (late stage, dry or wet disease) and 37 control patients. Each subject underwent a complete ophthalmologic examination at the time of sample collection. TaqMan gene copy number assays were conducted in technical quadruplicate for relative quantification of copy number variation in AMD vs. control patients.
Comparison of both GSTM1 and GSTM5 copy numbers between AMD vs. controls revealed no significant differences. GSTM5 copy number was two in all samples, and GSTM1 copy number ranged from 0-4, confirming the presence of deletions, but the deletions were not correlated with AMD status in this cohort, (mean copy number: AMD 1.14 vs. control 1.47, p = 0.24). A subgroup analysis of heterozygous deletions with a single GSTM1 copy number, likewise, did not correlate with AMD status, (number of samples: AMD 2, control 5, p = 0.88). There was a greater amount of GSTM1 duplications with copy numbers of 3 or 4 in control samples vs. AMD patient, although the relative percentage of each was small, (copy number of 3: AMD 2, Control 3, 5.7% of samples; copy number of 4: AMD 1, control 3, 4.6% of samples).
The reduced levels of both mRNA and protein of GSTM1 and GSTM5 we have previously found correlated with AMD disease state does not appear to be due to genomic deletion in this study population. The evidence presented suggests that the reduced amount of these antioxidants in AMD retinas may be due to another form of expression repression. Diminished levels of these enzymes in AMD retinas may increase susceptibility to oxidative stress.
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