The association of genetic variants of type 2 diabetes with kidney function.

MedStar author(s):
Citation: Kidney International. 82(2):220-5, 2012 Jul.PMID: 22513821Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Meta-Analysis | Multicenter Study | Research Support, N.I.H., ExtramuralSubject headings: *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]Year: 2012Local holdings: Available online from MWHC library: 1972 - present, Available in print through MWHC library: 1999 - 2006ISSN:
  • 0085-2538
Name of journal: Kidney internationalAbstract: 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.All authors: Best LG, Cochran BJ, Cole SA, Dyer TD, Franceschini N, Haack K, Howard BV, Laston S, Lee ET, Maccluer JW, North KE, Shara NM, Umans JG, Voruganti VS, Wang HFiscal year: FY2013Digital Object Identifier: Date added to catalog: 2013-09-17
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 22513821 Available 22513821

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.

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