TY  - BOOK
AU  - Howard, Barbara V
AU  - Shara, Nawar M
AU  - Umans, Jason G
AU  - Wang, Hong
TI  - The association of genetic variants of type 2 diabetes with kidney function
SN  - 0085-2538
PY  - 2012///
KW  - *Diabetes Mellitus, Type 2/ge [Genetics]
KW  - *Diabetic Nephropathies/ge [Genetics]
KW  - *Glomerular Filtration Rate/ge [Genetics]
KW  - *Kidney/pp [Physiopathology]
KW  - *Polymorphism, Single Nucleotide
KW  - Age of Onset
KW  - Aged
KW  - Albuminuria/ge [Genetics]
KW  - Albuminuria/pp [Physiopathology]
KW  - Biological Markers/ur [Urine]
KW  - Creatinine/ur [Urine]
KW  - Cross-Sectional Studies
KW  - Diabetes Mellitus, Type 2/eh [Ethnology]
KW  - Diabetic Nephropathies/eh [Ethnology]
KW  - Diabetic Nephropathies/pp [Physiopathology]
KW  - Female
KW  - Gene Frequency
KW  - Genetic Predisposition to Disease
KW  - Genome-Wide Association Study
KW  - Humans
KW  - Indians, North American/ge [Genetics]
KW  - Kidney/me [Metabolism]
KW  - Linear Models
KW  - Linkage Disequilibrium
KW  - Longitudinal Studies
KW  - Male
KW  - Membrane Proteins/ge [Genetics]
KW  - Middle Aged
KW  - Phenotype
KW  - Prospective Studies
KW  - Risk Assessment
KW  - Risk Factors
KW  - United States/ep [Epidemiology]
KW  - MedStar Health Research Institute
KW  - Journal Article
KW  - Meta-Analysis
KW  - Multicenter Study
KW  - Research Support, N.I.H., Extramural
N1  - Available online from MWHC library: 1972 - present, Available in print through MWHC library: 1999 - 2006
N2  - Type 2 diabetes is highly prevalent and is the major cause of progressive chronic kidney disease in American Indians. Genome-wide association studies identified several loci associated with diabetes but their impact on susceptibility to diabetic complications is unknown. We studied the association of 18 type 2 diabetes genome-wide association single-nucleotide polymorphisms (SNPs) with estimated glomerular filtration rate (eGFR; MDRD equation) and urine albumin-to-creatinine ratio in 6958 Strong Heart Study family and cohort participants. Center-specific residuals of eGFR and log urine albumin-to-creatinine ratio, obtained from linear regression models adjusted for age, sex, and body mass index, were regressed onto SNP dosage using variance component models in family data and linear regression in unrelated individuals. Estimates were then combined across centers. Four diabetic loci were associated with eGFR and one locus with urine albumin-to-creatinine ratio. A SNP in the WFS1 gene (rs10010131) was associated with higher eGFR in younger individuals and with increased albuminuria. SNPs in the FTO, KCNJ11, and TCF7L2 genes were associated with lower eGFR, but not albuminuria, and were not significant in prospective analyses. Our findings suggest a shared genetic risk for type 2 diabetes and its kidney complications, and a potential role for WFS1 in early-onset diabetic nephropathy in American Indian populations
UR  - http://dx.doi.org/10.1038/ki.2012.107
ER  -