Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes.
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.


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.
Sivenius
Katariina
K
Department of Clinical Nutrition, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. ksiveniu@hytti.uku.fi
Pihlajamäki
Jussi
J
Partanen
Juhani
J
Niskanen
Leo
L
Laakso
Markku
M
Uusitupa
Matti
M
D000449:Aldehyde Reductase / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000235:genetics*; D005260:Female; D005387:Finland; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012016:Reference Values
D000449:Aldehyde Reductase