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NDT Advance Access originally published online on July 28, 2006
Nephrology Dialysis Transplantation 2006 21(11):3122-3126; doi:10.1093/ndt/gfl434
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Cellular basis of diabetic nephropathy: IV Antioxidant enzyme mRNA expression levels in skin fibroblasts of type 1 diabetic sibling pairs

Maria Luiza Caramori1,2, Youngki Kim1, Paola Fioretto3, Chunmei Huang1, Stephen S. Rich4, Michael E. Miller4, Gregory B. Russell4 and Michael Mauer1

1Department of Pediatrics and 2Department of Medicine, University of Minnesota, Minnesota, USA, 3Department of Medical and Surgical Sciences, University of Padova, Italy and 4Department of Public Health Sciences, Wake Forest School of Medicine, North Carolina, USA

Correspondence and offprint requests to: Michael Mauer, M.D. 420 Delaware Street S.E, Mayo Mail Code 491, Minneapolis, MN 55455, USA. Email: mauer002{at}umn.edu

Background. Blunted cultured skin fibroblast (SF) antioxidant enzyme responses to hyperglycaemia are associated with diabetic nephropathy risk. The present study explores whether this association is, at least in part, genetically determined.

Methods. We measured glomerular structure and SF mRNA expression for catalase and glutathione peroxidase in 21 sibling pairs concordant for type 1 diabetes. All patients had four or more (mean 21.5) years of diabetes and glomerular filtration rate >40 ml/min/1.73 m2. Thirty-four patients were normoalbuminuric, four were microalbuminuric, three were proteinuric and one was not classifiable. Heritability of patient characteristics was assessed by intra-class correlation and by a genetic variance component model.

Results. Mesangial fractional volume, mesangial matrix fractional volume, glomerular basement membrane width and surface density of peripheral glomerular basement membrane per glomerulus were significantly correlated in these sibling pairs. Catalase mRNA expression levels were also related and highly heritable in these sibling pairs. The association between sibship and glutathione peroxidase mRNA expression levels did not reach statistical significance.

Conclusions. This study suggests that SF catalase mRNA expression levels, known to be associated with diabetic nephropathy risk, are in part genetically determined.

Keywords: genetics of diabetic nephropathy; glomerular structure; type 1 diabetes


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