%0 Journal Article
%T Genetic variation of Glucose Transporter-1 (GLUT1) and albuminuria in 10,278 European Americans and African Americans: a case-control study in the Atherosclerosis Risk in Communities (ARIC) Study
%A Charles C Hsu
%A Wenhong L Kao
%A Michael W Steffes
%A Tejal Gambir
%A Frederick L Brancati
%A Charles W Heilig
%A Alan R Shuldiner
%A Eric A Boerwinkle
%A Josef Coresh
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-16
%X A two-stage case-control study was nested in a prospective cohort study of 2156 African Americans and 8122 European Americans with urinary albumin-to-creatinine ratio(ACR). Cases comprised albuminuria(N = 825; ¡Ý 30 ¦Ìg/mg) and macroalbuminuria(N = 173; ¡Ý 300 ¦Ìg/mg). ACR < 30 ¦Ìg/mg classified controls(n = 9453). Logistic regression and odds ratios(OR) assessed associations. The evaluation phase(stage 1, n = 2938) tested associations of albuminuria(n = 305) with six GLUT1 SNPs: rs841839, rs3768043, rs2297977, Enh2(rs841847) XbaI(rs841853), and rs841858. Enh2 was examined separately in the replication phase(stage 2, n = 7340) and the total combined sample (n = 10,278), with all analyses stratified by race and type 2 diabetes.In European Americans, after adjusting for diabetes and other GLUT1 SNPs in stage 1, Enh2 risk genotype(TT) was more common in albuminuric cases(OR = 3.37, P = 0.090) whereas XbaI (OR = 0.94, p = 0.931) and remaining SNPs were not. In stage 1, the Enh2 association with albuminuria was significant among diabetic European Americans(OR = 2.36, P = 0.025). In African Americans, Enh2 homozygosity was rare(0.3%); XbaI was common(18.0% AA) and not associated with albuminuria. In stage 2(n = 7,340), Enh2 risk genotype had increased but non-significant OR among diabetic European Americans(OR = 1.66, P = 0.192) and not non-diabetics(OR = 0.99, p = 0.953), not replicating stage 1. Combining stages 1 and 2, Enh2 was associated with albuminuria(OR 2.14 [1.20-3.80], P = 0.009) and macroalbuminuria(OR 2.69, [1.02-7.09], P = 0.045) in diabetic European Americans. The Enh2 association with macroalbuminuria among non-diabetic European Americans with fasting insulin(OR = 1.84, P = 0.210) was stronger at the highest insulin quartile(OR = 4.08, P = 0.040).As demonstrated with type 1 diabetic nephropathy, the GLUT1 Enh2 risk genotype, instead of XbaI, may be associated with type 2 diabetic albuminuria among European Americans, though an association is not conclusive. The
%U http://www.biomedcentral.com/1471-2350/12/16