Cellular basis of diabetic nephropathy: IV. Antioxidant enzyme mRNA expression levels in skin fibroblasts of type 1 diabetic sibling pairs.
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.
Caramori
Maria Luiza
ML
Department of Pediatrics, University of Minnesota, M.D. 420 Delaware Street S.E, Mayo Mail Code 491, Minneapolis, MN 55455, USA.
Kim
Youngki
Y
Fioretto
Paola
P
Huang
Chunmei
C
Rich
Stephen S
SS
Miller
Michael E
ME
Russell
Gregory B
GB
Mauer
Michael
M
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D035781:Siblings; D012867:Skin / Q000166:cytology / Q000201:enzymology*
D000975:Antioxidants; D012333:RNA, Messenger; D002374:Catalase; D005979:Glutathione Peroxidase