title: Mitochondrial DNA haplogroups associated with age-related macular degeneration.
abstract: OBJECTIVE
  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.affiliation: Department of Ophthalmology, University of California Irvine, Orange, California 92868, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Udar
authors.forename: Shari R
authors.initials: SR
authors.lastname: Atilano
authors.forename: Masood
authors.initials: M
authors.lastname: Memarzadeh
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.forename: Marilyn
authors.initials: M
authors.lastname: Chwa
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lu
authors.forename: Barak
authors.initials: B
authors.lastname: Maguen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Langberg
authors.forename: Pinar
authors.initials: P
authors.lastname: Coskun
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Nesburn
authors.forename: Nikan
authors.initials: N
authors.lastname: Khatibi
authors.forename: Dieter
authors.initials: D
authors.lastname: Hertzog
authors.forename: Khoi
authors.initials: K
authors.lastname: Le
authors.forename: Daniel
authors.initials: D
authors.lastname: Hwang
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Kenney
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial