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Aldose Reductase Gene Polymorphisms and Peripheral Nerve Function in Patients With Type 2 Diabetes

¹ Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
² Department of Medicine, University of Kuopio, Kuopio, Finland
³ Department of Clinical Neurophysiology, University of Kuopio, Kuopio, Finland

Address correspondence and reprint requests to Katariina Sivenius, MD, Department of Clinical Nutrition, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. E-mail: ksiveniu{at}hytti.uku.fi

OBJECTIVE—We screened the human aldose reductase (ALR) gene for DNA sequence variants in type 2 diabetic and nondiabetic subjects and investigated whether the previously reported and novel polymorphisms were associated with neurophysiologic deterioration and clinical peripheral neuropathy.

RESEARCH DESIGN AND METHODS—The study population included 85 Finnish type 2 diabetic and 126 nondiabetic subjects. The genetic analyses were performed using the PCR, single-strand conformation polymorphism, restriction fragment-length polymorphism, and automated laser fluorescence scanning analyses. A detailed neurologic examination and neurophysiologic analyses were performed at the time of diagnosis and at the 10-year examination.

RESULTS—The genetic screening identified four polymorphisms: C-106T, C-11G, A11370G, and C19739A. The C and Z-2 alleles of the C-106T polymorphism and the previously reported (CA)_n repeat marker were more frequent in type 2 diabetic subjects than in nondiabetic subjects. At baseline, the diabetic subjects with the T allele of the C-106T polymorphism had lower sensory response amplitude values in the peroneal (P = 0.025), sural (P = 0.007), and radial (P = 0.057) nerves and, during follow-up, a greater decrease in the conduction velocity of the motor peroneal nerve than those with the C-106C genotype. No associations were found between the polymorphisms examined and clinical polyneuropathy.

CONCLUSIONS—The C-106T polymorphism of the ALR gene may contribute to an early development of neurophysiologic deterioration in type 2 diabetic patients.

Abbreviations: ALR, aldose reductase • NCV, nerve conduction velocity • RA, response amplitude • RFLP, restriction fragment-length polymorphism • SSCP, single-strand conformation polymorphism

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