29b1c366-e3c6-4acf-9204-41a914591ccd
title
Association between variation in the actin-binding gene  caldesmon  and diabetic nephropathy in type 1 diabetes.
2726c178-67ac-4834-8225-f028b94d9cd1
abstract
Dysfunction of the actin cytoskeleton is a key event in the pathogenesis of diabetic nephropathy. We previously reported that certain cytoskeletal genes are upregulated in mesangial cells exposed to a high extracellular glucose concentration. One such gene,  caldesmon , lies on chromosome 7q35, a region linked to nephropathy in family studies, making it a candidate susceptibility gene for diabetic nephropathy. We screened all exons, untranslated regions, and a 5-kb region upstream of the gene for variation using denaturing high-performance liquid chromatography technology.  An A>G single nucleotide polymorphism (SNP) at position -579  in the promoter region was associated with nephropathy in a case-control study using 393 type 1 diabetic patients from Northern Ireland (odds ratio [OR] 1.38, 95% CI 1.02-1.86, P = 0.03). A similar trend was found in an independent sample from a second center. When the sample groups were combined (n = 606), the association between the  -579G  allele and nephropathy remained significant (OR 1.35, 1.07-1.70, P = 0.01). The haplotype structure in the surrounding 7-kb region was determined. No single haplotype was more strongly associated with nephropathy than the  -579A>G  SNP. These results suggest a role for the  caldesmon  gene in susceptibility to diabetic nephropathy in type 1 diabetes.