TITLE

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

AUTHOR(S)
Yamasaki, Hiroshi; Sasaki, Hideyuki; Ogawa, Kenichi; Shono, Takeshi; Tamura, Shinobu; Doi, Asako; Sasahara, Miyoshi; Kawashima, Hiromichi; Nakao, Taisei; Furuta, Hiroto; Nishi, Masahiro; Nanjo, Kishio
PUB. DATE
April 2006
SOURCE
Diabetes Care;Apr2006, Vol. 29 Issue 4, p888
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
20443259

 

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