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Diabetes Care 29:888-894, 2006
DOI: 10.2337/diacare.29.04.06.dc05-1984
© 2006 by the American Diabetes Association
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Pathophysiology/Complications
Original Article

Uncoupling Protein 2 Promoter Polymorphism –866G/A Affects Peripheral Nerve Dysfunction in Japanese Type 2 Diabetic Patients

Hiroshi Yamasaki, MD, Hideyuki Sasaki, MD, PHD, Kenichi Ogawa, MD, PHD, Takeshi Shono, MD, Shinobu Tamura, MD, PHD, Asako Doi, PHD, Miyoshi Sasahara, MD, PHD, Hiromichi Kawashima, MD, PHD, Taisei Nakao, MD, PHD, Hiroto Furuta, MD, PHD, Masahiro Nishi, MD, PHD and Kishio Nanjo, MD, PHD

From The First Department of Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan

Address correspondence and reprint requests to Hideyuki Sasaki, The First Department of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, Japan. E-mail: sasaki-h{at}wakayama-med.ac.jp

OBJECTIVE—To determine genetic predispositions for diabetic polyneuropathy, we investigated the relationship between the –866G/A polymorphism of uncoupling protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—We first examined whether UCP2 mRNA had been expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism –866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who were subjected to nerve conduction, quantitative vibratory perception, head-up tilt, and heart rate variability tests, by PCR restriction fragment–length polymorphism. The relationships between UCP2 genotype and various nerve functions were analyzed by uni- and multivariable analysis.

RESULTS—Expression of UCP2 mRNA was confirmed in rat DRG. Multiple regression analysis clarified the hypothesis that the G/A + A/A genotype was significantly related to decreased motor nerve conduction velocity and impaired blood pressure maintenance on the head-up tilt test. Multiple logistic regression analysis revealed that the G/A + A/A genotypes are a significant risk factor for sensory nerve conduction slowing and orthostatic hypotension.

CONCLUSIONS—UCP2 promoter gene polymorphism –866 G/A was significantly associated with nerve conduction slowing and vasomotor sympathetic functions. These findings suggest that the higher UCP2 activity related to the A allele has an energy-depleting effect on peripheral nerve function in type 2 diabetic patients.

Abbreviations: {Delta}BP, change in systolic blood pressure after standing for 5 min • CMAP, compound muscle action potential • DPN, diabetic peripheral neuropathy • DRG, dorsal root ganglion • MCV, motor nerve conduction velocity • ROS, reactive oxygen species • SCV, sensory nerve conduction velocity • SNAP, sensory nerve action potential • UCP, uncoupling protein • VPT, vibratory perception threshold • VPT-F, VPT at tip of index finger • VPT-T, VTP at tip of big toe


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Copyright © 2006 by the American Diabetes Association.