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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.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.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.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.

Type

Journal article

Journal

Molecular vision

Publication Date

01/2012

Volume

18

Pages

657 - 674

Addresses

Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands.

Keywords

Humans, Macular Degeneration, Eye Proteins, Case-Control Studies, Cohort Studies, Gene Frequency, Haplotypes, Heterozygote, Homozygote, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, European Continental Ancestry Group, United States, Germany, Netherlands, Female, Male, Glucose Transporter Type 1, Genetic Association Studies