PURPOSE: To examine the mtDNA control regions in normal and age-related macular degeneration (AMD) retinas. To identify the mtDNA variations associated with AMD. METHODS: Retinas from 10 normal and 11 AMD globes were isolated and analyzed for mtDNA rearrangements by long extension-polymerase chain reaction (LX-PCR) and for the nature and frequency of single-nucleotide polymorphisms (SNPs) in the mtDNA control region by direct sequencing. Blood DNA was extracted from 99 AMD and 92 age-matched control subjects. The sequence variations that define haplogroups H, I, J, K, T, V, X, and U were characterized by PCR, restriction enzyme digestion, and/or sequencing. RESULTS: LX-PCR of retinal mtDNAs revealed high levels of rearrangements in the patients with AMD and the control subjects, consistent with the decline in mitochondrial function with age. However, the AMD retinas had higher oxidized DNA levels and a higher number of SNPs than controls (P = 0.02). The control region SNPs T16126C and A73G, commonly found in haplogroups J and T, were more frequent in the AMD retinas than in normal retinas. The associations between AMD and haplogroups J and T were confirmed and extended by analysis of blood DNA. SNPs at position a T16126C (J; odds ratio [OR] = 3.66), T16126C+G13368A (JT; OR = 10.27), A4917G+A73G (T4; OR = 5), and T3197C+A12308G (U5; OR = infinity), were all strongly associated with AMD. CONCLUSIONS: AMD retinas exhibited increased mtDNA control region SNPs compared to normal retinas. This correlated with an increased frequency of mtDNA SNPs associated with haplogroups J, T and U in patients with AMD. These results implicate mitochondrial alterations in the etiology of AMD.
PURPOSE: To examine the mtDNA control regions in normal and age-related macular degeneration (AMD) retinas. To identify the mtDNA variations associated with AMD. METHODS: Retinas from 10 normal and 11 AMD globes were isolated and analyzed for mtDNA rearrangements by long extension-polymerase chain reaction (LX-PCR) and for the nature and frequency of single-nucleotide polymorphisms (SNPs) in the mtDNA control region by direct sequencing. Blood DNA was extracted from 99 AMD and 92 age-matched control subjects. The sequence variations that define haplogroups H, I, J, K, T, V, X, and U were characterized by PCR, restriction enzyme digestion, and/or sequencing. RESULTS: LX-PCR of retinal mtDNAs revealed high levels of rearrangements in the patients with AMD and the control subjects, consistent with the decline in mitochondrial function with age. However, the AMD retinas had higher oxidized DNA levels and a higher number of SNPs than controls (P = 0.02). The control region SNPs T16126C and A73G, commonly found in haplogroups J and T, were more frequent in the AMD retinas than in normal retinas. The associations between AMD and haplogroups J and T were confirmed and extended by analysis of blood DNA. SNPs at position a T16126C (J; odds ratio [OR] = 3.66), T16126C+G13368A (JT; OR = 10.27), A4917G+A73G (T4; OR = 5), and T3197C+A12308G (U5; OR = infinity), were all strongly associated with AMD. CONCLUSIONS:AMD retinas exhibited increased mtDNA control region SNPs compared to normal retinas. This correlated with an increased frequency of mtDNA SNPs associated with haplogroups J, T and U in patients with AMD. These results implicate mitochondrial alterations in the etiology of AMD.
Authors: Haijiang Lin; Haifeng Xu; Fong-Qi Liang; Hao Liang; Praveena Gupta; Anna N Havey; Michael E Boulton; Bernard F Godley Journal: Invest Ophthalmol Vis Sci Date: 2011-06-01 Impact factor: 4.799
Authors: Monique D Courtenay; John R Gilbert; Lan Jiang; Anna C Cummings; Paul J Gallins; Laura Caywood; Lori Reinhart-Mercer; Denise Fuzzell; Claire Knebusch; Renee Laux; Jacob L McCauley; Charles E Jackson; Margaret A Pericak-Vance; Jonathan L Haines; William K Scott Journal: Hum Genet Date: 2011-07-13 Impact factor: 4.132
Authors: M Cristina Kenney; Marilyn Chwa; Shari R Atilano; Payam Falatoonzadeh; Claudio Ramirez; Deepika Malik; Mohamed Tarek; Javier Cáceres Del Carpio; Anthony B Nesburn; David S Boyer; Baruch D Kuppermann; Marquis P Vawter; S Michal Jazwinski; Michael V Miceli; Douglas C Wallace; Nitin Udar Journal: Biochim Biophys Acta Date: 2013-11-04