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P. Sternberg, J. A. Canter, L. M. Olson, K. Spencer, M. A. Hauser, S. Schmidt, E. A. Postel, M. A. Pericak-Vance, A. Agarwal, J. L. Haines; Mitochondrial DNA Polymorphism A4917G Is Independently Associated With Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):243.
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Mitochondria play central roles in energy production, free radical production, and apoptosis. The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD).
AMD patients and unrelated controls were ascertained at both Vanderbilt University Medical Center (VUMC) and Duke University Medical Center (DUMC). All patients and controls had complete ophthalmoscopic exams. Mitochondrial genotyping was performed by the 5'nuclease allelic discrimination Taqman assay, using single nucleotide polymorphisms (SNPs). Effect size for the association is measured as odds ratio (OR) with 95% confidence intervals.
A preliminary study of 393 individuals (293 cases and 100 controls) revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs 9.0%, p=0.11). Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting 280 tightly age-matched Caucasian pairs from an existing large AMD study population. This well-characterized population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR=2.16, 95%CI 1.20 - 3.91, p=0.01).
A specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.
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