Inflammation is a recognized mechanism underlying the pathogenesis of renal dysfunction in type 1 diabetes. Evidence suggests that genetic factors modulate the expression of inflammatory genes, which may lead to an enhanced predisposition to developing renal complications in patients with diabetes. In this study, we examined 55 genetic variants from 16 human candidate inflammatory genes for associations with renal function expressed as the estimated glomerular filtration rate in 1540 participants from the Genetics of Kidneys in Diabetes study.
View Article and Find Full Text PDFCNDP1 is located on 18q22.3, where linkage with diabetic nephropathy has been observed in several populations, including Pima Indians. However, evidence for association between CNDP1 alleles and diabetic nephropathy is equivocal and population-dependent.
View Article and Find Full Text PDFDepending on the scope of the research project, categories of single-nucleotide polymorphism (SNP) genotyping experiments range from low to medium to high throughput, with each approach differing widely in cost, platform, and efficiency. Medium-throughput genotyping is generally appropriate for assaying up to 36 markers in 384 individuals and is commonly used for fine-mapping chromosomal regions identified in genome scans. Multiplexing, which allows for simultaneous assessment of multiple SNPs, is an efficient, rapid, and economic way to augment medium-throughput genotyping output and is readily performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).
View Article and Find Full Text PDFVariants 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.
View Article and Find Full Text PDFObjective: End-stage renal disease (ESRD) attributed to diabetes is strongly dependent on genetic factors. We previously reported association between variants in the plasmacytoma variant translocation gene (PVT1) and ESRD attributed to type 2 diabetes in Pima Indians. The objective of this study was to evaluate the extent to which these variants mediate susceptibility in other populations.
View Article and Find Full Text PDFTo identify genetic variants contributing to end-stage renal disease (ESRD) in type 2 diabetes, we performed a genome-wide analysis of 115,352 single nucleotide polymorphisms (SNPs) in pools of 105 unrelated case subjects with ESRD and 102 unrelated control subjects who have had type 2 diabetes for > or =10 years without macroalbuminuria. Using a sliding window statistic of ranked SNPs, we identified a 200-kb region on 8q24 harboring three SNPs showing substantial differences in allelic frequency between case and control pools. These SNPs were genotyped in individuals comprising each pool, and strong evidence for association was found with rs2720709 (P = 0.
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