Functional Polymorphisms of UCP2 and UCP3 Are Associated With a Reduced Prevalence of Diabetic Neuropathy in Patients With Type 1 Diabetes
- Gottfried Rudofsky, Jr, MD,
- Antonia Schroedter,
- Andreas Schlotterer, PHD,
- Olga E. Voron’ko, PHD,
- Martin Schlimme, PHD,
- Joerg Tafel, MD,
- Berend H. Isermann, MD,
- Per M. Humpert, MD,
- Michael Morcos, MD,
- Angelika Bierhaus, PHD,
- Peter P. Nawroth, MD and
- Andreas Hamann, MD
- Division of Endocrinology and Metabolism, Department of Medicine, University of Heidelberg, Heidelberg, Germany
- Address correspondence and reprint requests to Andreas Hamann, MD, Division of Endocrinology and Metabolism, Department of Medicine, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. E-mail: andreas_hamann{at}med.uni-heidelberg.de
Abstract
OBJECTIVE—We studied the association between polymorphisms in the UCP genes and diabetes complications in patients with type 1 diabetes.
RESEARCH DESIGN AND METHODS—We analyzed 227 patients with type 1 diabetes using PCR and subsequent cleavage by restriction endonucleases for the promoter variants A-3826G in the UCP1 gene, G-866A in the UCP2 gene, and C-55T in the UCP3 gene.
RESULTS—No effect of the A-3826G polymorphism in the UCP1 gene on diabetes complications was found. Patients who were heterozygous or homozygous for the G-866A polymorphism in the UCP2 gene or the C-55T polymorphism in the UCP3 gene had a significantly reduced prevalence of diabetic neuropathy (UCP2: odds ratio 0.44 [95% CI 0.24–0.79], P = 0.007; UCP3: 0.48 [0.25–0.92], P = 0.031), whereas there was no association with other diabetes complications. This effect was stronger when G-866A and C-55T occurred in a cosegregatory manner (UCP2 and UCP3: 0.28 [0.12–0.65], P = 0.002). Furthermore, a multiple logistic regression model showed an age- and diabetes duration–independent effect of the cosegregated polymorphisms on the prevalence of diabetic neuropathy (P = 0.013).
CONCLUSIONS—Our data indicate that both the G-866A polymorphism in the UCP2 gene and the C-55T polymorphism in the UCP3 gene are associated with a reduced risk of diabetic neuropathy in type 1 diabetes. Thus, the results presented here support the hypothesis that higher expression of uncoupling protein might prevent mitochondria-mediated neuronal injury and, ultimately, diabetic neuropathy.
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted September 28, 2005.
- Received April 28, 2005.
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