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01 April 2010

Manganese superoxide dismutase (MnSOD) gene (Ala-9Val, Ile58Thr) polymorphism in patients with age-related macular degeneration (AMD)

Michal KowalskiABCD, Anna Bielecka -KowalskaBCD, Katarzyna OszajcaABCD, Eusebio Makandjou -OlaDE, Piotr JaworskiB, Jacek BartkowiakDE, Janusz SzemrajBCDEFG

Med Sci Monit 2010; 16(4): CR190-196 :: ID: 878501

Abstract

Background
Oxidative stress is involved in the pathogenesis of many chronic disorders including cancer, inflammation, and neurologic diseases. Reactive oxygen species (ROS) may play a major role in age-related macular degeneration (AMD). This study investigated the mRNA and protein profiles of manganese superoxide dismutase MnSOD in patients with AMD and healthy controls, while examining its genetic sequence polymorphism (Ala-9Val, Ile58Thr). Our intent was to find a correlation between the expression of MnSOD genes and nucleotide sequence polymorphisms encoded in the gene of the dry and wet form of AMD.
Material and Method
We examined 300 unrelated AMD patients and 300 unrelated healthy controls who gave free consent to participate in the study. The MnSOD gene polymorphisms were determined by PCR/RFLP method. We also used real-time RT-PCR and ELISA methods to estimate expression of MnSOD mRNA and protein.
Results
There were statistically significant differences in the genotype distribution between patients with AMD and controls. Our results showed positive correlations between gene sequence polymorphism and the level of MnSOD mRNA and protein expression. The Ala-9Ala genotype and alanine allele (Ala-9Val sequence polymorphism) is much more frequent in AMD patients than in healthy subjects. Healthy controls who are homozygotes Val/Val and heterozygotes Ala/Val showed lower expression of the MnSOD gene as compared to homozygote Ala/Ala. The lowest expression of MnSOD (homozygotes Val/Val and heterozygotes Ala/Val for wet and dry form of AMD) was noted in patients with AMD.
Conclusions
These data suggest a genetic role of MnSOD polymorphism in the development of age-related degeneration.

Keywords: Threonine - genetics, Superoxide Dismutase - genetics, RNA, Messenger - metabolism, Polymorphism, Genetic, Polymorphism, Restriction Fragment Length, Polymerase Chain Reaction, Models, Genetic, Macular Degeneration - genetics, Isoleucine - genetics, Enzyme-Linked Immunosorbent Assay - methods, Case-Control Studies, Alanine - genetics, Valine - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750