Role of aldose reductase C-106T polymorphism among diabetic Egyptian patients with different microvascular complications

Nermine Hossam Zakaria, Salah Ahmed Marzouk, Abla Ahmed Abou Zeid, Eman Saeed Gharaff


The aldose reductase pathway proves that elevated blood glucose promotes cellular dysfunction. The polyol pathway converts excess intracellular glucose into alcohols via activity of the aldose reductase. This enzyme catalyzes the conversion of glucose to sorbitol which triggers variety of intracellular changes in the tissues. Among diabetes, activity is drastically increased in association with three main consequences inside the cells. The aim of this study was to detect the association of the C-106 T polymorphism of the aldose reductase gene and its frequency among a sample of 150 Egyptian adults with type 2 diabetic patients having diabetic microvascular. The detection of the aldose reductase C-106 T polymorphism gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype distribution of the C-106 T polymorphism showed that CC genotype was statistically significantly higher among patients with retinopathy compared to nephropathy. Patients with nephropathy had significant association with the TT genotype when compared with diabetic retinopathy patients. Follow up study after the genotype detection among recently diagnosed diabetic patients in order to give a prophylactic aldose reductase inhibitors; studying the microvascular complications and its relation to the genotype polymorphisms. The study may include multiple gene polymorphisms to make the relation between the gene and the occurrence of these complications more evident.


AGE: advanced glycation end products PCR-RFLP(polymerase chain reaction–restriction fragment length polymorphism ALR ( Aldose reductase )

Full Text:



Graham A, Brown L, Hedge PG, et al. Structure of human aldose reductase gene. J Biol Chem 268:6872-6877, 1993.

Srivastava SK, Ramana KV, Bhatnagar A. Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. Endocr Rev 380–392, 2005.

Shmizu H, Ohtani KI, Tsuchiya T, et al. Aldose reductase Mrna expression is associated with rapid development of diabetic microangiopathy in Japanese type 2 diabetic (T2DM) patients. Diabetes Nutr Metab 13:75-79, 2000.

Wang K, Bohren KM, Gabbay KH. Characterization of human aldose reductase gene promoter. J Biol Chem 268:16052-16058, 1993.

Spite M, Baba SP, Ahmed Y, et al. Substrate specificity and catalytic efficiency of aldo-keto reductases with phospholipid aldehydes. Biochem J 405:95-105, 2007.

Bain BJ, Bates I. Basic haematological techniques. In Lewis SM, Bain BJ, Bates I, eds. Dacie and Lewis Practical Haematology, 10th edition. Churchill Livingstone Publishers, pp 25-57, 2006.

Lamb E, Newman DJ, Price CP. Kidney Function Tests. In: Burtis CA, Ashwood ER, Bruns DE, eds. Tietz Text book of Clinical Chemistry and Molecular Diagnostics, 4th edition. Elsevier Saunders, pp 797-826, 2006.

Eckfeldt JH, Bruns DE. Another step towards standardization of methods for measuring hemoglobin A1 C. Clin Chem 43:1811-1813, 1997.

Stamp R J, Simpson R D. Simple screening tests for detection of microalbuminuria. Pract Diabetes Int 5: 248-250, 1988.

MacGregor LC, Rosecan LR, Laties AM. Altered retinal metabolism in diabetes. I. Microanalysis of lipid, glucose, sorbitol, and myo-inositol in the choroid and in the individual layers of the retina. J Biol Chem 261:4046-4051, 1986.

Olmos P, Bast¬as MJ, Vollrath V et al. C(-106)T polymorphism of the aldose reductase gene and the progression rate of diabetic retinopathy. Diabetse Res Clin Pract 74(2):175-82, 2006.

Spoelstra JA, Stolk RP, de Bruyne MC, et al. Factors associated with switching from oral hypoglycaemic agents to insulin therapy. Netherlands J Med 60:243-248, 2002.

Sivenius K, Aki JP, Partanen J, et al, Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes. Diabetes Care 27: 9-12, 2004.

Sinha S, Guleria R, Misra A, et al. Pulmonary functions in patients with type 2 diabetes mellitus and correlation with anthropometry and microvascular complications. Indian J Med Res 119; 66-71, 2004.

Shera AS, Jawad F, Maqsood A, Jamal S, Azfar M, Ahmed U. Prevalence of chronic complications and associated factors in type 2 diabetes. J Pak Med Assoc 54:54-59, 2004.

Womack L, Peters D, Barrett EJ, et al. Abnormal skeletal muscle capillary recruitment during exercise in patients with type 2 diabetes mellitus and microvascular complications. J Am Coll Cardiol 53: 2175-2183, 2009.

Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk L, Jozwiak L. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients. Nephrol Dial Transplant 22: 827-32, 2007.

Yingwang Y, Maggie CY, Shao-chin LE, et al. Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes. Diabetes Care 26:2410-2415, 2003.

Gerrits EG, Lutgers HL, Kleefstra N, et al. Skin autofluorescence: a tool to identify type 2 diabetic patients at risk for developing microvascular complications. Diabetes Care 31:517-521, 2008.

Hsiao FC, Lee CH, Hung YJ, et al. The Relationship between plasma glucose concentration and hemoglobin A1c during a standardized meal tolerance test in individuals with type 2 diabetes. J Med Sci 28: 9-14, 2008.

Bonakdaran S, Hami M, Shakeri M. Hyperuricemia and albuminuria in patients with type 2 diabetes mellitus. Iranian J Kidney Dis 5:21-26, 2011.

Zhang X, Saaddine JB, Chou CF, et al. Prevalence of Diabetic Nephropathy in the united states, 2005-2008. JAMA 304: 649-56, 2010.

Gosek K, Moczulski D, Zukowska-Szczechowska E, Grzeszczak W. C-106T Polymorphism in promoter of aldose reductase gene is a risk factor for diabetic nephropathy in type 2 diabetes patients with poor glycaemic control. Nephron Exp Nephrol 99:e63-e67, 2005.

Watarai A, Nakashima E, Hamada Y, et al. Aldose reductase gene is associated with diabetic macroangiopathy in Japanese type 2 diabetic patients. Diabet Med 23: 894-899, 2006.

Olmos P, Bast¬as MJ, Vollrath V et al. C(-106)T polymorphism of the aldose reductase gene and the progression rate of diabetic retinopathy. Diabetes Res Clin Pract 74:175-182, 2006.

Katakami N, Kaneto H, Takahara M, et al. Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 15: 8-9, 2011.

Demaine A, Cross D, Millward A. Polymorphisms of the aldose reductase gene and susceptibility to retinopathy in type 1 diabetes mellitus. Invest Ophtalmol Vis Sci 2011; 1: 1552-83.


  • There are currently no refbacks.