title: Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study.
abstract: BACKGROUND
  Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170).
  
  
  METHODS
  Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene.
  
  
  RESULTS
  The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background.
  
  
  CONCLUSIONS
  There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD.
authors.affiliation: Gavin Herbert Eye Institute, Univeresity of California Irvine, Hewitt Hall, Room 2028, 843 Health Science Rd, Irvine, CA 92697, USA. mkenney@uci.edu
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Kenney
authors.forename: Dieter
authors.initials: D
authors.lastname: Hertzog
authors.forename: Garrick
authors.initials: G
authors.lastname: Chak
authors.forename: Shari R
authors.initials: SR
authors.lastname: Atilano
authors.forename: Nikan
authors.initials: N
authors.lastname: Khatibi
authors.forename: Kyaw
authors.initials: K
authors.lastname: Soe
authors.forename: Andrew
authors.initials: A
authors.lastname: Nobe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yang
authors.forename: Marilyn
authors.initials: M
authors.lastname: Chwa
authors.forename: Feilin
authors.initials: F
authors.lastname: Zhu
authors.forename: Masood
authors.initials: M
authors.lastname: Memarzadeh
authors.forename: Jacqueline
authors.initials: J
authors.lastname: King
authors.forename: Jonathan
authors.initials: J
authors.lastname: Langberg
authors.forename: Kent
authors.initials: K
authors.lastname: Small
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Nesburn
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.forename: Nitin
authors.initials: N
authors.lastname: Udar
mesh_terms: D000368:Aged; D002140:California; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D008268:Macular Degeneration / Q000208:ethnology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial