Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 30% of individuals with type 1 and type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk for cardiovascular and other microvascular complications. Diabetes and kidney diseases rank within the top 10 causes of death in Westernized countries and cause significant morbidity. Given these observations, genetic, genomic, and proteomic investigations have been initiated to better define basic mechanisms for disease initiation and progression, to identify individuals at risk for diabetic complications, and to develop more efficacious therapies. In this review we have focused on linkage analyses of candidate genes or chromosomal regions, or coarse genome-wide scans, which have mapped either categorical (chronic kidney disease or end-stage renal disease) or quantitative kidney traits (albuminuria/proteinuria or glomerular filtration rate). Most loci identified to date have not been replicated, however, several linked chromosomal regions are concordant between independent samples, suggesting the presence of a diabetic nephropathy gene. Two genes, carnosinase (CNDP1) on 18q, and engulfment and cell motility 1 (ELMO1) on 7p14, have been identified as diabetic nephropathy susceptibility genes, but these results require authentication. The availability of patient data sets with large sample sizes, improvements in informatics, genotyping technology, and statistical methodologies should accelerate the discovery of valid diabetic nephropathy susceptibility genes.
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PMID:Mining the genome for susceptibility to diabetic nephropathy: the role of large-scale studies and consortia. 1741 89

Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been associated with kidney disease attributed to type 2 diabetes. The Pima Indians of Arizona have high rates of diabetic nephropathy, which is strongly dependent on genetic determinants; thus, we sought to investigate the role of ELMO1 polymorphisms in mediating susceptibility to this disease in this population. Genotype distributions were compared among 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships, and 107 cases with diabetic ESRD and 108 controls with long duration diabetes and no nephropathy. We sequenced 17.4 kb of ELMO1 and identified 19 variants. We genotyped 12 markers, excluding those in 100% genotypic concordance with other variants or with a minor allele frequency <0.05, plus 21 additional markers showing association with ESRD in earlier studies. In the family study, the strongest evidence for association was with rs1345365 (odds ratio [OR]=2.42 per copy of A allele [1.35-4.32]; P=0.001) and rs10951509 (OR=2.42 per copy of A allele [1.31-4.48]; P=0.002), both of which are located in intron 13 and are in strong pairwise linkage disequilibrium (r(2)=0.97). These associations were in the opposite direction from those observed in African Americans, which suggests that the relationship between diabetic kidney disease and ELMO1 variation may involve as yet undiscovered functional variants or complex interactions with other biological variables.
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PMID:ELMO1 variants and susceptibility to diabetic nephropathy in American Indians. 2082