Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 PLA(2)R1 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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PMID:Chronic kidney disease: novel insights from genome-wide association studies. 2169 Nov 25

Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in individuals with diabetes, and it is the leading cause of end-stage renal disease (ESRD) worldwide. Stanniocalcin-1 (STC-1) is present in various tissues, and it has antioxidant and anti-apoptotic activities, which play a role in kidney protection, including diabetic nephropathy (DN). However, the mechanism that underlies these effects remains unknown. This study suggests that STC-1 ameliorates oxidative stress and cell apoptosis in the kidneys of db/db mice and high glucose (HG)-treated BUMPT cells by inhibiting Bnip3 expression through AMPK/Sirt3 pathway activation. In the clinic, DKD patients with high levels of STC-1 have a better prognosis than patients with low STC-1 levels. Thus, we concluded that STC-1 ameliorates renal injury in DN by inhibiting the expression of Bnip3 through the AMPK/SIRT3 pathway and that serum STC-1 is independently associated with DKD progression in patients with type 2 diabetes. As high STC-1 levels indicate a better prognosis, synthetic STC-1 may become a potential drug for the treatment of DKD patients.
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PMID:STC-1 ameliorates renal injury in diabetic nephropathy by inhibiting the expression of BNIP3 through the AMPK/SIRT3 pathway. 3068 4