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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Association between variation in the actin-binding gene caldesmon and diabetic nephropathy in type 1 diabetes.

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.[1]


  1. Association between variation in the actin-binding gene caldesmon and diabetic nephropathy in type 1 diabetes. Conway, B.R., Maxwell, A.P., Savage, D.A., Patterson, C.C., Doran, P.P., Murphy, M., Brady, H.R., Fogarty, D.G. Diabetes (2004) [Pubmed]
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