title: Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration.
abstract: 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). A preliminary study of 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt 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 Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study), we were able to match 560 (280 cases and 280 unaffected) on exact age at examination. This study 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). In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.
authors.affiliation: Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. jeff.canter@vanderbilt.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Canter
authors.forename: Lana M
authors.initials: LM
authors.lastname: Olson
authors.forename: Kylee
authors.initials: K
authors.lastname: Spencer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schnetz-Boutaud
authors.forename: Brent
authors.initials: B
authors.lastname: Anderson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.forename: Eric A
authors.initials: EA
authors.lastname: Postel
authors.forename: Anita
authors.initials: A
authors.lastname: Agarwal
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Paul
authors.initials: P
authors.lastname: Sternberg
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
mesh_terms: D000225:Adenine; D000368:Aged; D000375:Aging / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D016678:Genome; D006147:Guanine; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D044465:White People
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers; D004272:DNA, Mitochondrial; D006147:Guanine; D000225:Adenine