Assocation 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.

Relevance of heterometallic binding energy for metal underpotential deposition

We present first-principles calculations for a number of metals adsorbed on several different metallic substrates. Some of these systems are very relevant in electrochemistry, especially in the field of underpotential deposition phenomena. The present studies reveal the existence of a relationship between the excess binding energy and the surface energy difference between substrate and adsorbate. Comparisons with experimental underpotential shifts show that excess binding energies are systematically underestimated. By analyzing experimental information on different systems, we conclude that this discrepancy between our vacuum calculations and experiments carried out in an electrolytic solution is likely to be due to anion adsorption and/or solvent effects.