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

To identify genetic elements that might confer susceptibility to diabetic nephropathy, we performed a genome-wide analysis of gene-based single nucleotide polymorphisms (SNPs) in a large cohort of Japanese patients with diabetes. In case-control association studies, patients with type 2 diabetes were divided into two groups, one having retinopathy as well as overt nephropathy and the other (the control group) having diabetic retinopathy but with no signs of renal involvement. Genotyping of these patients at >55,000 SNP loci indicated a gene encoding solute carrier family 12 member 3 (SLC12A3) to be a good candidate for the susceptibility to diabetic nephropathy, in view of a significant association of one landmark SNP located in the 24th intron (chi(2) = 15.4, P = 0.000087, odds ratio = 2.53 [95% CI 1.57-4.09]). Subsequent analysis of additional genetic variations in this gene identified several SNPs that were significantly associated with nephropathy, especially one in exon 23 (+78 G to A: Arg913Gln, chi(2) = 18.5, P = 0.00002, odds ratio = 2.53 [95% CI 1.64-3.90]). The results implicated that substitution of Arg913 to Gln in the SLC12A3 gene might reduce the risk to develop diabetic nephropathy and suggested that the gene product might be a potential target for the prevention or treatment of this disease.
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PMID:Association of solute carrier family 12 (sodium/chloride) member 3 with diabetic nephropathy, identified by genome-wide analyses of single nucleotide polymorphisms. 1457 5

Diabetic nephropathy is a serious complication of diabetes and the leading cause of end-stage renal disease. Studies indicate both environmental and genetic factors contribute to the development and progression of diabetic nephropathy. In particular, epidemiological evidence shows a familial clustering of nephropathy in siblings with diabetes, supporting an important role of genetic susceptibility in the pathogenesis of diabetic nephropathy. A common approach in genetic research is assessment of candidate gene polymorphisms using case-control analysis; a number of studies have evaluated predictable candidate genes for diabetic nephropathy. In contrast, only a few studies have used a whole genome approach, such as scanning of micro-satellite markers, in the assessment of genetic susceptibility to diabetic nephropathy. A whole genome linkage analysis using families of Pima Indians showed susceptibility loci for diabetic nephropathy on chromosome 3, 7, and 20. Another linkage analysis using discordant sib-pairs of Caucasian families with type 1 diabetes identified a critical area on chromosome 3q. However, these results have been inconclusive and further investigation is required. Recently, a genome-wide, case-control analysis identifying susceptibility genes for diabetic nephropathy was performed. As a result, a single nucleotide polymorphism in exon 23 of the solute carrier family 12 (sodium-chloride cotransporter) member 3 gene was found to be strongly associated with diabetic nephropathy. Although further assessment of this polymorphism is needed, this strategy offers great promise in the identification of genetic factors predisposing patients to diabetic nephropathy. Identification of genetic susceptibility markers may offer new hope in the diagnosis and treatment of diabetic nephropathy.
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PMID:Assessing genetic susceptibility to diabetic nephropathy. 1617 81

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD). Genetic susceptibility plays an important role in the development and progression of diabetic nephropathy. Previous studies have revealed that polymorphisms in the SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) gene, which encodes solute carrier family 12 member 3, might contribute to genetic susceptibility to diabetic nephropathy and essential hypertension. In this study, we examined whether the SLC12A3 gene locus is associated with ESRD resulting from diabetic nephropathy. We genotyped 11 common single nucleotide polymorphisms (SNPs) in the SLC12A3 gene in 177 patients with ESRD due to type 2 diabetes and 184 patients with diabetic retinopathy but with no signs of renal involvement. Three SNPs (g.34372G>A [Arg913Gln], g.39143G>A, and g.41727C>T) were found to be associated with ESRD due to diabetic nephropathy. These three SNPs were in complete linkage disequilibrium. Haplotype 4 in block 2 (18806C, 21822C, 34372A, 39143A, 39240T, 39375C, and 41727T) showed a significant association with ESRD due to type 2 diabetes (P = 0.0028). These results suggest that the SLC12A3 gene locus is associated with ESRD due to diabetic nephropathy.
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PMID:SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) polymorphisms are associated with end-stage renal disease in diabetic nephropathy. 1650 53