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. 2016;41(3):410-6.
doi: 10.3109/02713683.2015.1016179. Epub 2015 Apr 21.

GSTM1 and GSTM5 Genetic Polymorphisms and Expression in Age-Related Macular Degeneration

Allan A Hunter 3rd  1 , Zeljka Smit-McBride  1 , Rachel Anderson  1 , Matthew H Bordbari  1 , Gui-shuang Ying  2 , Esther S Kim  1 , Susanna S Park  1 , David G Telander  1 , Joshua L Dunaief  2 , Leonard M Hjelmeland  1 , Lawrence S Morse  1
Affiliations

GSTM1 and GSTM5 Genetic Polymorphisms and Expression in Age-Related Macular Degeneration

Allan A Hunter 3rd et al. Curr Eye Res. 2016.

Abstract

Purpose: Previously, two cytosolic antioxidant enzymes, Glutathione S-transferase Mu 1 (GSTM1) and Mu 5 (GSTM5), were reduced in retinas with age-related macular degeneration (AMD). This study compared genomic copy number variations (gCNV) of these two antioxidant enzymes in AMD versus controls.

Methods: Genomic copy number (gCN) assays were performed using Taqman Gene Copy Number Assays (Applied Biosystems, Darmstadt, Germany) in technical quadruplicate for both GSTM1 and GSTM5. Peripheral leukocyte RNA levels were compared with controls in technical triplicates. Statistical comparisons were performed in SAS v9.2 (SAS Institute Inc., Cary, NC).

Results: A large percentage of patients in both AMD and age-matched control groups had no copies of GSTM1 (0/0). The mean gCN of GSTM1 was 1.40 (range 0-4) and 1.61 (range 0-5) for AMD and control, respectively (p = 0.29). A greater percentage of control patients had > 3 gCNs of GSTM1 compared with AMD, respectively (15.3% versus 3.0%, p = 0.004). The gCN of GSTM5 was 2 in all samples except one control sample. The relative quantification of GSTM1 and GSTM5 mRNA from peripheral blood leukocytes in patients showed significant differences in relative expression in AMD versus control (p < 0.05). Peripheral blood leukocyte mRNA and gCN were not significantly correlated (p = 0.27).

Conclusion: Since high copy numbers of GSTM1 are found more frequently in controls than in AMD, it is possible that high copy number leads to increased retinal antioxidant defense. Genomic polymorphisms of GSTM1 and GSTM5 do not significantly affect the peripheral blood leukocyte mRNA levels.

Keywords: Age-related macular degeneration (AMD); expression repression; genomic copy number; glutathione-S-transferase; oxidative stress.

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References

    1. Gaillard ER, Atherton SJ, Eldred G, Dillon J. Photophysical studies on human retinal lipofuscin. Photochem Photobiol. 1995;61(5):448–53. Epub 1995/05/01. - PubMed
    1. Rozanowska M, Jarvis-Evans J, Korytowski W, Boulton ME, Burke JM, Sarna T. Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species. J Biol Chem. 1995;270(32):18825–30. Epub 1995/08/11. - PubMed
    1. Martinez-Lara E, Siles E, Hernandez R, Canuelo AR, Luisa del Moral M, Jimenez A, et al. Glutathione S-transferase isoenzymatic response to aging in rat cerebral cortex and cerebellum. Neurobiology of aging. 2003;24(3):501–9. Epub 2003/02/26. - PubMed
    1. Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000;45(2):115–34. Epub 2000/10/18. - PubMed
    1. Mirza S, Plafker KS, Aston C, Plafker SM. Expression and distribution of the class III ubiquitin-conjugating enzymes in the retina. Mol Vis. 2010;16:2425–37. Epub 2010/12/09. - PMC - PubMed

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