Gene link to diabetic nephropathy
doi:10.1038/nindia.2012.91 Published online 22 June 2012
New research has shown that genetic variation in the promoter region of the osteopontin (OPN) gene increases levels of osteopontin protein in renal cells of Asian Indians suffering from type 2 diabetes. This causes damage to glomeruli, the filters of the kidneys, resulting in diabetic nephropathy. The OPN protein might therefore be a good candidate as a biomarker for diabetic nephropathy in type 2 diabetes.
Diabetic nephropathy is the leading cause of end-stage renal disease. Studies have shown that only 30–35% of diabetic patients develop progressive diabetic nephropathy irrespective of glycemic control, which indicates the involvement of genetic factors.
Studies have also shown increased levels of OPN protein in the kidneys of humans and mice with diabetes and glomerular damage. However, these studies had not established a genetic link between OPN levels and diabetic nephropathy in diabetic patients of Asian and North Indian origin.
To investigate this link, the researchers selected 1,115 diabetic patients and divided them into two groups. The first consisted of 240 patients with diabetic nephropathy and 255 type 2 diabetic patients without nephropathy; the second consisted of 405 patients with diabetic nephropathy and 215 type 2 diabetic patients without nephropathy. The researchers also analysed genomic DNA isolated from the patients' peripheral blood lymphocytes.
The study identified a genetic variation in a single-nucleotide polymorphism in the promoter region of the OPN gene. This variation causes a threefold increase in the risk factor for diabetic nephropathy in type 2 diabetic patients in Asian Indians. This single-nucleotide polymorphism affects the transcription and expression of OPN gene, thus causing enhanced proteinuria leading to progressive deterioration of kidney function.
"Because this single-nucleotide polymorphism affects OPN transcription activity, it may influence renal OPN levels. Thus, newer therapies targeting OPN need to be investigated in diabetic nephropathy," says lead researcher Madhu Khullar.
The authors of this work are from: Department of Experimental Medicine and Biotechnology, Department of Nephrology, and Department of Endocrinology, Post Graduate Institute of Medicine Education & Research, Chandigarh, India and Department of Clinical Sciences—Diabetes and Endocrinology, Lund University Diabetes Centre, Clinical Research Centre, (CRC), University Hospital Skane (UMAS), Malmo, Sweden.
- Cheema, B. S. et al. Association of an Osteopontin gene promoter polymorphism with susceptibility to diabetic nephropathy in Asian Indians. Clin. Chim. Acta. doi: 10.1016/j.cca.2012.04.028 (2012)