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      The Decorin Gene 179 Allelic Variant Is Associated with a Slower Progression of Renal Disease in Patients with Type 1 Diabetes

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          Background genetic factors may influence the variability in the rate of progression of kidney disease in type 1 diabetes. In diabetes, progressive mesangial matrix expansion and glomerular sclerosis are, to a large extent, mediated by TGF-β1. Decorin, a proteoglycan which is a component of the extracellular matrix, regulates TGF-β1 activity and expression. We have examined the relationship between the 179/183/185 polymorphism of the Decorin gene and the progression of diabetic nephropathy. Methods: From a cohort of 175 European patients with diabetic nephropathy, we studied 79 patients who were selected because they had a follow-up of at least 2 years (average 6.5 years; range: 2.5–15 years), and regular measurements of serum creatinine on 5 or more occasions. Creatinine clearance (CrCl) calculated from serum creatinine concentration was used as a measure of derived glomerular filtration rate (dGFR). All patients were on antihypertensive therapy. Results: The rate of dGFR decline in the whole cohort was [median (range)] 4.6 (–3.8 to 18) ml/min/year. No patient with 185 allele was found. Patients with 179/183 and 179/179 genotype (n = 14), who were considered together and named 179 carriers, had a slower rate of GFR decline [2.1 (0.06–11.7) ml/min/year] as compared to patients with Decorin 183/183 genotype (n = 65) [5.6 (–3.8 to 18) ml/min/year; p < 0.001]. In addition, when considering individual data, patients carrying the 179 allele had a 3.0 (95%CI: 1.8–4.2)-fold higher probability to be slow progressors (i.e. GFR decline below the median). This difference could not be accounted for by differences in duration of disease, type and duration of antihypertensive therapy, albumin excretion rate, blood glucose or blood pressure control. In a multivariate logistic analysis albumin excretion rate (p < 0.001), mean arterial pressure (p = 0.07) and Decorin gene polymorphism (p = 0.036), but not HbA1c, were independently correlated with the rate of dGFR fall. Conclusion: The 179 allele variant of the Decorin gene is related to a slower progression of DN in type 1 diabetic patients with albuminuria and receiving antihypertensive therapy.

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          Most cited references 5

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          Pathophysiology of progressive nephropathies.

           T Bertani,  G. Remuzzi (1998)
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            Negative regulation of transforming growth factor-beta by the proteoglycan decorin.

            Decorin is a small chondroitin-dermatan sulphate proteoglycan consisting of a core protein and a single glycosaminoglycan chain. Eighty per cent of the core protein consists of 10 repeats of a leucin-rich sequence of 24 amino acids. Similar repeats have been found in two other proteoglycans, biglycan and fibromodulin, and in several other proteins including Drosophila morphogenetic proteins. Expression of high levels of decorin in Chinese hamster ovary cells has a dramatic effect on their morphology and growth properties. We now report that this effect is due at least in part to the ability of decorin to bind transforming growth factor-beta, an autocrine factor that stimulates the growth of Chinese hamster ovary cells. As transforming growth factor-beta induces synthesis of decorin in many cell types, our results suggest that decorin may be a component of a feedback system regulating cell growth.
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              Genetics of diabetic nephropathy: evidence for major and minor gene effects.

               A Krolewski (1999)

                Author and article information

                S. Karger AG
                September 2002
                14 August 2002
                : 92
                : 1
                : 72-76
                aClinicaland Research Unit of Endocrinology, Scientific Institute ‘Casa Sollievo della Sofferenza’ San Giovanni Rotondo (FG); bDiabetes Unit, Hospital ‘Brotzu’, Cagliari; cChair of Metabolic Medicine, University of Padova, Padova; dInstitute of Internal Medicine, Turin, Italy; eUnit for Metabolic Medicine, Department of Endocrinology Diabetes and Internal Medicine, GKT School of Medicine, King’s College London, Guy’s Hospital, London, UK; fDepartment of Clinical Science, University ‘La Sapienza’, Rome, Italy
                64470 Nephron 2002;92:72–76
                © 2002 S. Karger AG, Basel

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                Figures: 1, Tables: 1, References: 29, Pages: 5
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