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 m 2. 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.
Bibliographical noteFunding Information:
Acknowledgements. Dr Caramori was supported by the Foundation for the Coordination of Higher Education and Graduate Training (CAPES) from the Brazilian Government and by a Research Fellowship grant from the Juvenile Diabetes Research Foundation International (JDRFI). Dr Fioretto was a recipient of a JDRFI Research Fellowship grant and Career Development Award. Dr Huang was supported by a mentor-based fellowship grant from the American Diabetes Association. This work was supported by grants from National Institute of Health (DK 13083 and DK 54638) and National Center for Research Resources (M01-RR00400). We thank Mr Thomas Groppoli for performing the morphometric studies and Mr Paul Walker for helping with the RT–PCR studies.
- Genetics of diabetic nephropathy
- Glomerular structure
- Type 1 diabetes