|Title||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.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Hsu CC, Kao WL, Steffes MW, Gambir T, Brancati FL, Heilig CW, Shuldiner AR, Boerwinkle EA, Coresh J|
|Journal||BMC Med Genet|
|Date Published||2011 Jan 19|
|Keywords||African Americans, Albuminuria, Case-Control Studies, Diabetes Mellitus, European Continental Ancestry Group, Genetic Variation, Genome-Wide Association Study, Glucose Transporter Type 1, Humans, Molecular Epidemiology, Polymorphism, Single Nucleotide, United States|
BACKGROUND: Evidence suggests glucose transporter-1 (GLUT1) genetic variation affects diabetic nephropathy and albuminuria. Our aim was to evaluate associations with albuminuria of six GLUT1 single nucleotide polymorphisms(SNPs), particularly XbaI and the previously associated Enhancer-2 (Enh2) SNP.
METHODS: 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; ≥ 30 μg/mg) and macroalbuminuria (N = 173; ≥ 300 μg/mg). ACR
RESULTS: 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).
CONCLUSIONS: 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 association among diabetic European Americans found in stage 1 was not replicated in stage 2; however, this risk association was evident after combining all diabetic European Americans from both stages. Additionally, our results suggest this association may extend to non-diabetics with high insulin concentrations. Rarity of the Enh2 risk genotype among African Americans precludes any definitive conclusions, although data suggest a risk-enhancing role.
|Alternate Journal||BMC Med Genet|
|PubMed Central ID||PMC3034664|
|Grant List||N01-HC-55022 / HC / NHLBI NIH HHS / United States |
N01-HC-55016 / HC / NHLBI NIH HHS / United States
P30 DK079637 / DK / NIDDK NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States