Category:

Novel Therapeutic,Diagnostic,Research Tool

Description:

Diabetic nephropathy is the leading cause of end stage renal disease in the Western world and develops in about one-third of diabetic patients.  Although, several established risk factors such as duration of diabetes, hyperglycemia and hypertension have been shown to increase the risk to develop nephropathy, they do not solely account for the incidence and progression of diabetic nephropathy. Rather, there is growing evidence that the risk to develop diabetic nephropathy is in large part genetically determined. Although the evidence for genetic susceptibility in the pathogenesis of diabetic nephropathy is well-recognized, the causative genes remained to be identified.

Connective tissue growth factor (CTGF) is known to be an important risk factor in diabetic nephropathy.  CTGF is increased in diabetic nephropathy and correlates with the degree of albuminuria (leaking of albumin into urine, an early indicator of renal dysfunction). Researchers at the Medical University of South Carolina recently discovered a novel single nucleotide polymorphism (SNP) in the promoter region of the CTGF gene that predisposes diabetic subjects to develop albuminuria (an early indicator of kidney dysfunction). The researchers conducted a study based on cross-sectional data generated from the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC)-cohort of type 1 diabetic patients.

The novel CTGF SNP is associated with a 3-fold increased risk to develop albuminuria compared to diabetic patients without the SNP. Survival analyses demonstrated that the onset of albuminuria occurs at a more rapid rate in diabetic subjects with the polymorphism than without the polymorphism. Functional studies show that the basal activity of the mutant was significantly higher than wildtype. The novel SNP is located in one of the Smad 1 binding sites and functional analyses indicate that this region is critical for Smad1-dependent transcriptional regulation of the CTGF gene.

Potential Applications:

• First test of its kind.
• Test for diabetic patients under consideration for intensive v.s. standard glycemic control, blood pressure regulation, and treatment with ACE inhibitors.
• Those positive for the polymorphism could be considered for intensive or alternative treatment.

Inventor(s):

Dr. A.A. Jaffa, Dr. L.M. Luttrell

Relevent Publications:

Jaffa AA, et al; J Clin Endocrinol Metab. 2008 ;93(5):1893-900.

Patent Status:

Application to be filed (MUSC-FRD #P0917)

Availability:

Available for:
exclusive
non-exclusive
licensing.

Technology Status:

in vitro data; in vivo data (862 human subjects genotyped)

Licensing Contact:

Ryan N. Fiorini, Ph.D., MBA, MHA
MUSC Foundation for Research Development
PO Box 250828
Charleston, SC 29425
843.876.1906
fiorinir@musc.edu