Uncoupling protein 2 promoter polymorphism -866G/A affects peripheral nerve dysfunction in Japanese type 2 diabetic patients.
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.


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.
The First Department of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, Japan.
Hiroshi
H
Yamasaki
Hideyuki
H
Sasaki
Kenichi
K
Ogawa
Takeshi
T
Shono
Shinobu
S
Tamura
Asako
A
Doi
Miyoshi
M
Sasahara
Hiromichi
H
Kawashima
Taisei
T
Nakao
Hiroto
H
Furuta
Masahiro
M
Nishi
Kishio
K
Nanjo
D000483:Alleles; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007473:Ion Channels; D007564:Japan; D016015:Logistic Models; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D051381:Rats; D020318:Rats, Long-Evans; D012044:Regression Analysis; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2