TY - JOUR
T1 - Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration
AU - Baas, Dominique C.
AU - Ho, Lintje
AU - Tanck, Michael W. T.
AU - Fritsche, Lars G.
AU - Merriam, Joanna E.
AU - van Het Slot, Ruben
AU - Koeleman, Bobby P. C.
AU - Gorgels, Theo G. M. F.
AU - van Duijn, Cornelia M.
AU - Uitterlinden, André G.
AU - de Jong, Paulus T. V. M.
AU - Hofman, Albert
AU - ten Brink, Jacoline B.
AU - Vingerling, Johannes R.
AU - Klaver, Caroline C. W.
AU - Dean, Michael
AU - Weber, Bernhard H. F.
AU - Allikmets, Rando
AU - Hageman, Gregory S.
AU - Bergen, Arthur A. B.
PY - 2012
Y1 - 2012
N2 - Purpose: 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 Wurzburg (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
AB - Purpose: 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 Wurzburg (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
M3 - Article
C2 - 22509097
SN - 1090-0535
VL - 18
SP - 657
EP - 674
JO - Molecular vision
JF - Molecular vision
IS - 72
ER -