Review: Genetics of diabetic nephropathy

Maeda, Shiro

doi:10.1177/1753944708094768

Cited by 19 publications

(16 citation statements)

References 84 publications

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“…In general, these results did not closely overlap genomic regions implicated in previous non-FIND linkage studies for DN [5] (online suppl. table S1).…”

Section: Discussionsupporting

confidence: 48%

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Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

et al. 2011

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Background: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. Methods: A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Results: Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10^–5, LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. Conclusion: These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN.

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“…In general, these results did not closely overlap genomic regions implicated in previous non-FIND linkage studies for DN [5] (online suppl. table S1).…”

Section: Discussionsupporting

confidence: 48%

“…Genetic factors contribute to risk of DN in all ethnic groups [4,5]. Genomewide linkage scans of kidney function in the presence of DM implicated regions on chromosomes 3q, 7p, 7q, 9, 10q and 18q (online suppl.…”

Section: Introductionmentioning

confidence: 99%

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

et al. 2011

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“…Albuminuria, chronic kidney disease (CKD), and ESRD segregate within diabetic families, but DN develops only in a subset of T2D-affected populations in all race groups [95,96]. Also, there is a racial affinity with DN, which further underscores the presence of genetic and/or environmental risk factors.…”

Section: Diabetic Nephropathymentioning

confidence: 99%

Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications

Murea

Ma²,

Freedman³

2012

Rev Diabet Stud

290

188

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Faced with a global epidemic of type 2 diabetes (T2D), it is critical that researchers improve our understanding of the pathogenesis of T2D and related vascular complications. These findings may ultimately lead to novel treatment options for disease prevention or delaying progression. Two major paradigms jointly underlie the development of T2D and related coronary artery disease, diabetic nephropathy, and diabetic retinopathy. These paradigms include the genetic risk variants and behavioral/environmental factors. This article systematically reviews the literature supporting genetic determinants in the pathogenesis of T2D and diabetic vasculopathy, and the functional implications of these gene variants on the regulation of beta-cell function and glucose homeostasis. We update the discovery of diabetes and diabetic vasculopathy risk variants, and describe the genetic technologies that have uncovered them. Also, genomic linkage between obesity and T2D is discussed. There is a complementary role for behavioral and environmental factors modulating the genetic susceptibility and diabetes risk. Epidemiological and clinical data demonstrating the effects of behavioral and novel environmental exposures on disease expression are reviewed. Finally, a succinct overview of recent landmark clinical trials addressing glycemic control and its impact on rates of vascular complications is presented. It is expected that novel strategies to exploit the gene-and exposure-related underpinnings of T2D will soon result.

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“…Another approach investigated the association between common genetic variants (minor allele frequencies 1 5% in the general population) in plausible candidate genes and kidney function or disease phenotypes such as diabetic nephropathy [11,34] . However, confirmatory replication was rarely achieved due to a multitude of study design issues such as inadequate power, low significance threshold, and differences in phenotype definition between studies [35] .…”

Section: The Evolving Methodology In Genetic Researchmentioning

confidence: 99%

Chronic Kidney Disease: Novel Insights from Genome-Wide Association Studies

Böger¹,

Heid²

2011

Kidney Blood Press Res

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Chronic kidney disease (CKD) is common, affecting about 10% of the general population, and causing significant morbidity and mortality. Apart from the risk conferred by traditional cardiovascular risk factors, there is a strong genetic component. The method of a genome-wide association study (GWAS) is a powerful hypothesis-free approach to unravel this component by association analyses of CKD with several million genetic variants distributed across the genome. Since the publication of the first GWAS in 2005, this method has led to the discovery of novel loci for numerous human common diseases and phenotypes. Here, we review the recent successes of meta-analyses of GWAS on renal phenotypes. UMOD, SHROOM3, STC1, LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2/SH2B3, DACH1, UBE2Q2, and SLC7A9 were uncovered as loci associated with estimated glomerular filtration rate (eGFR) and CKD, and CUBN as a locus for albuminuria in cross-sectional data of general population studies. However, less than 1.5% of the total variance of eGFR and albuminuria is explained by the identified variants, and the relative risk for CKD is modified by at most 20% per locus. In African Americans, much of the risk for end-stage nondiabetic kidney disease is explained by common variants in the MYH9/APOL1 locus, and in individuals of European descent, variants in HLA-DQA1 and PLA₂R1 implicate most of the risk for idiopathic membranous nephropathy. In contrast, genetic findings in the analysis of diabetic nephropathy are inconsistent. Uncovering variants explaining more of the genetically determined variability of kidney function is hampered by the multifactorial nature of CKD and different mechanisms involved in progressive CKD stages, and by the challenges in elucidating the role of low-frequency variants. Meta-analyses with larger sample sizes and analyses of longitudinal renal phenotypes using higher-resolution genotyping data are required to uncover novel loci associated with severe renal phenotypes.

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Review: Genetics of diabetic nephropathy

Cited by 19 publications

References 84 publications

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications

Chronic Kidney Disease: Novel Insights from Genome-Wide Association Studies

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