The association of genetic variants of type 2 diabetes with kidney function.
The association of genetic variants of type 2 diabetes with kidney function.
- 2012
Available online from MWHC library: 1972 - present, Available in print through MWHC library: 1999 - 2006
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.
English
0085-2538
*Diabetes Mellitus, Type 2/ge [Genetics]
*Diabetic Nephropathies/ge [Genetics]
*Glomerular Filtration Rate/ge [Genetics]
*Kidney/pp [Physiopathology]
*Polymorphism, Single Nucleotide
Age of Onset
Aged
Albuminuria/ge [Genetics]
Albuminuria/pp [Physiopathology]
Biological Markers/ur [Urine]
Creatinine/ur [Urine]
Cross-Sectional Studies
Diabetes Mellitus, Type 2/eh [Ethnology]
Diabetic Nephropathies/eh [Ethnology]
Diabetic Nephropathies/pp [Physiopathology]
Female
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Indians, North American/ge [Genetics]
Kidney/me [Metabolism]
Linear Models
Linkage Disequilibrium
Longitudinal Studies
Male
Membrane Proteins/ge [Genetics]
Middle Aged
Phenotype
Prospective Studies
Risk Assessment
Risk Factors
United States/ep [Epidemiology]
MedStar Health Research Institute
Journal Article
Meta-Analysis
Multicenter Study
Research Support, N.I.H., Extramural
Available online from MWHC library: 1972 - present, Available in print through MWHC library: 1999 - 2006
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.
English
0085-2538
*Diabetes Mellitus, Type 2/ge [Genetics]
*Diabetic Nephropathies/ge [Genetics]
*Glomerular Filtration Rate/ge [Genetics]
*Kidney/pp [Physiopathology]
*Polymorphism, Single Nucleotide
Age of Onset
Aged
Albuminuria/ge [Genetics]
Albuminuria/pp [Physiopathology]
Biological Markers/ur [Urine]
Creatinine/ur [Urine]
Cross-Sectional Studies
Diabetes Mellitus, Type 2/eh [Ethnology]
Diabetic Nephropathies/eh [Ethnology]
Diabetic Nephropathies/pp [Physiopathology]
Female
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Indians, North American/ge [Genetics]
Kidney/me [Metabolism]
Linear Models
Linkage Disequilibrium
Longitudinal Studies
Male
Membrane Proteins/ge [Genetics]
Middle Aged
Phenotype
Prospective Studies
Risk Assessment
Risk Factors
United States/ep [Epidemiology]
MedStar Health Research Institute
Journal Article
Meta-Analysis
Multicenter Study
Research Support, N.I.H., Extramural