CUBN Is a Gene Locus for Albuminuria

Abstract
Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 × 10−11) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
- Copyright © 2011 by the American Society of Nephrology
In this issue
Jump to section
More in this TOC Section
Cited By...
- Hypertension and renin-angiotensin system blockers are not associated with expression of Angiotensin Converting Enzyme 2 (ACE2) in the kidney
- Genome-Wide Association Studies of CKD and Related Traits
- Integration of GWAS Summary Statistics and Gene Expression Reveals Target Cell Types Underlying Kidney Function Traits
- A cellular model of albumin endocytosis uncovers a link between membrane and nuclear proteins
- Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Kidney Disease-Related Genes in Patients with Diabetic Kidney Disease
- The Use of Mendelian Randomization to Determine the Role of Metabolic Traits on Urinary Albumin-to-Creatinine Ratio
- Bayesian multivariate reanalysis of large genetic studies identifies many new associations
- LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis
- Heart Disease and Stroke Statistics--2018 Update: A Report From the American Heart Association
- The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease
- The Benefits of Tubular Proteinuria: An Evolutionary Perspective
- Tonicity-Responsive Enhancer-Binding Protein Mediates Hyperglycemia-Induced Inflammation and Vascular and Renal Injury
- Lessons from CKD-Related Genetic Association Studies-Moving Forward
- Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United States
- Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study
- African Ancestry-Specific Alleles and Kidney Disease Risk in Hispanics/Latinos
- SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
- Mendelian Randomization as an Approach to Assess Causality Using Observational Data
- Challenges in Rare Variant Association Studies for Complex Kidney Traits: CFHR5 and IgA Nephropathy
- Beyond APOL1: Genetic Inroads into Understanding Population Disparities in Diabetic Kidney Disease
- Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans
- Proximal Tubules Have the Capacity to Regulate Uptake of Albumin
- APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults
- Genome-Wide Meta-Analyses of Plasma Renin Activity and Concentration Reveal Association With the Kininogen 1 and Prekallikrein Genes
- Sequencing of LRP2 Reveals Multiple Rare Variants Associated with Urinary Trefoil Factor-3
- Polygenic Overlap Between Kidney Function and Large Artery Atherosclerotic Stroke
- Prevalence of CKD and Its Relationship to eGFR-Related Genetic Loci and Clinical Risk Factors in the SardiNIA Study Cohort
- Cubilin Maintains Blood Levels of HDL and Albumin
- The Proximal Tubule and Albuminuria: Really!
- Microalbuminuria as a Risk Predictor in Diabetes: The Continuing Saga
- Generalizability of Genetic Findings Related to Kidney Function and Albuminuria
- Generalization of Associations of Kidney-Related Genetic Loci to American Indians
- Kidney Disease and Related Findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study
- Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- In Vivo Gene Expression Profiling of Retina Postintravitreal Injections of Dexamethasone and Triamcinolone at Clinically Relevant Time Points for Patient Care
- Exome Sequencing Reveals Cubilin Mutation as a Single-Gene Cause of Proteinuria