Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0005508
Title: Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration
Authors: SanGiovanni J.P.
Arking D.E.
Iyengar S.K.
Elashoff M.
Clemons T.E.
Reed G.F.
Henning A.K.
Sivakumaran T.A.
Xu X.
DeWan A.
Agr髇 E.
Rochtchina E.
Sue C.M.
Wang J.J. 
Mitchell P.
Hoh J.
Francis P.J.
Klein M.L.
Chew E.Y.
Chakravarti A.
Keywords: mitochondrial DNA
reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)
mitochondrial DNA
reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)
adult
aged
article
controlled study
female
gene locus
gene sequence
genetic analysis
genetic association
genetic variability
genotype
haplotype
human
inheritance
major clinical study
male
retina macula age related degeneration
risk assessment
single nucleotide polymorphism
age distribution
gene frequency
genetic predisposition
genetics
haplotype
middle aged
mutation
retina macula degeneration
sex ratio
Age Distribution
Aged
Aged, 80 and over
DNA, Mitochondrial
Electron Transport Complex I
Female
Gene Frequency
Genetic Predisposition to Disease
Haplotypes
Humans
Macular Degeneration
Male
Middle Aged
Mutation
Sex Distribution
Issue Date: 2009
Citation: SanGiovanni J.P., Arking D.E., Iyengar S.K., Elashoff M., Clemons T.E., Reed G.F., Henning A.K., Sivakumaran T.A., Xu X., DeWan A., Agr髇 E., Rochtchina E., Sue C.M., Wang J.J., Mitchell P., Hoh J., Francis P.J., Klein M.L., Chew E.Y., Chakravarti A. (2009). Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration. PLoS ONE 4 (5) : e5508. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0005508
Abstract: Background: Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been reported in large prospective cohorts. Methodology/Prinicipal Findings: We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease. In Stage I we resequenced the entire genome in 99 elderly AMD-free controls and 215 people with advanced AMD from the 12-year study. A consistent association with AMD in 14 of 17 SNPs characterizing the mtDNA T haplogroup emerged. Further analysis revealed these associations were driven entirely by the T2 haplogroup, and characterized by two variants in Complex I genes (A11812G of MT-ND4 and A14233G of MT-ND6). We genotyped T haplogroups in an independent sample of 490 cases and 61 controls from the same study (Stage II) and in 56 cases and 246 controls from the 10-year study (Stage III). People in the T2 haplogroup were approximately 2.5 times more likely to have advanced AMD than their peers (odds ratio [OR] = 2.54, 95%CI 1.36-4.80, P?0.004) after considering the totality of evidence. Findings persisted after considering the impact of AMD-associated variants A69S and Y402H (OR = 5.19, 95%CI 1.19-22.69, P?0.029). Conclusion: Loci defining the mtDNA T2 haplogroup and Complex I are reasonable targets for novel functional analyses and therapeutic research in AMD.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161839
ISSN: 19326203
DOI: 10.1371/journal.pone.0005508
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