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TheUCP1−3826A/G Polymorphism Is Associated with Diabetic Retinopathy and IncreasedUCP1andMnSOD2Gene Expression in Human Retina
- Source :
- Investigative Opthalmology & Visual Science. 53:7449
- Publication Year :
- 2012
- Publisher :
- Association for Research in Vision and Ophthalmology (ARVO), 2012.
-
Abstract
- PURPOSE Uncoupling protein 1 (UCP1) reduces mitochondrial production of reactive oxygen species (ROS). ROS overproduction is related to diabetic retinopathy (DR), a chronic complication of diabetes mellitus (DM). Therefore, deleterious polymorphisms in the UCP1 gene are candidate risk factors for DR. We investigated the relationships between the UCP1 -3826A/G polymorphism and risk of DR and UCP1 gene expression in human retina. Considering that superoxide dismutase-2 (MnSOD2) enzyme is the first line of defense against oxidative stress in mitochondria, we also analyzed MnSOD2 gene expression in retinal samples according to different UCP1 -3826A/G genotypes. METHODS In a case-control study, frequencies of -3826A/G polymorphisms were analyzed in 257 type 1 DM patients (154 cases with DR and 103 controls without DR). In a cross-sectional study comprising cadaveric cornea donors, UCP1 and MnSOD2 gene expressions were evaluated in 107 retinal samples differentiated according to different -3826A/G genotypes. RESULTS In the type 1 DM group, multivariate analysis confirmed that the G/G genotype was an independent risk factor for DR (OR = 3.503; P = 0.043). In cornea donors, G allele carriers had higher UCP1 cDNA and protein concentrations than A/A carriers (P = 0.034 and P = 0.039, respectively). Interestingly, G allele carriers exhibited increased MnSOD2 expression (P = 0.001). CONCLUSIONS This study suggests that the -3826A/G polymorphism is associated with DR in type 1 DM patients. This is the first report demonstrating UCP1 gene expression in human retinas and indicates that the -3826A/G polymorphism influences its expression. In addition, the -3826G allele was associated with increased MnSOD2 expression; thus, suggesting that this allele could be a marker of oxidative stress.
- Subjects :
- Adult
Male
DNA, Complementary
Gene Expression
Biology
Real-Time Polymerase Chain Reaction
medicine.disease_cause
Ion Channels
Retina
Mitochondrial Proteins
chemistry.chemical_compound
Gene Frequency
Diabetes mellitus
Gene expression
Genotype
medicine
Humans
Allele
Gene
Alleles
Uncoupling Protein 1
Retrospective Studies
Diabetic Retinopathy
Polymorphism, Genetic
Superoxide Dismutase
Retinal
Diabetic retinopathy
medicine.disease
Immunohistochemistry
Molecular biology
Oxidative Stress
Haplotypes
chemistry
Female
Oxidative stress
Follow-Up Studies
Subjects
Details
- ISSN :
- 15525783
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Investigative Opthalmology & Visual Science
- Accession number :
- edsair.doi.dedup.....ff58b4267fc148e01929c13fd494e405