title: Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress-mediated AMD pathology.
  
  
  METHODS
  Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Würzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed.
  
  
  RESULTS
  In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies.
  
  
  CONCLUSIONS
  No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists.
authors.affiliation: Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands.
authors.forename: Dominique C
authors.initials: DC
authors.lastname: Baas
authors.forename: Lintje
authors.initials: L
authors.lastname: Ho
authors.forename: Michael W T
authors.initials: MW
authors.lastname: Tanck
authors.forename: Lars G
authors.initials: LG
authors.lastname: Fritsche
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Merriam
authors.forename: Ruben
authors.initials: R
authors.lastname: van het Slot
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Theo G M F
authors.initials: TG
authors.lastname: Gorgels
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Jacoline B
authors.initials: JB
authors.lastname: ten Brink
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Hageman
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005858:Germany / Q000453:epidemiology; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology; D044465:White People
chemical_list: D005136:Eye Proteins; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human