This Article Full Text Full Text (PDF) All Versions of this Article: 90/2/1176    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bulotta, A. Articles by Trischitta, V. Search for Related Content PubMed PubMed Citation Articles by Bulotta, A. Articles by Trischitta, V. Related Collections Diabetes and Insulin

The Common –866G/A Polymorphism in the Promoter Region of the UCP-2 Gene Is Associated with Reduced Risk of Type 2 Diabetes in Caucasians from Italy

Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza (A.B., O.L., A.C., R.D.P., V.T.), San Giovanni Rotondo, Italy; Unit of Genetics, Scientific Institute Casa Sollievo della Sofferenza (A.Q., M.C.), San Giovanni Rotondo, Italy; Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud (F.P.), S. Maria Imbaro, Italy; Casa Sollievo della Sofferenza-Mendel Institute (S.P., V.T.), Rome, Italy; and Department of Clinical Sciences, University La Sapienza (V.T.), Rome, Italy

Address all correspondence and requests for reprints to: Dr. Angela Bulotta, Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy. E-mail: a.bulotta{at}operapadrepio.it.

Uncoupling protein-2 (UCP2) regulates insulin secretion and may play an important role in linking obesity to type 2 diabetes (T2D). Previous studies of the role of the UCP2 promoter –866G/A single nucleotide polymorphisms (SNP) in T2D have given opposite results. We tested the distribution of the –866G/A SNP in 746 T2D patients and 327 healthy unrelated Caucasians from Italy. We also tested for an effect of the P12A variant of the peroxisomal proliferator-activated receptor-2 (PPAR2) gene on diabetes risk given by the UCP2 SNP. Compared with –866G/G carriers, a progressively reduced (P = 0.01) risk of T2D was observed in –866G/A and –866A/A subjects, with the latter showing an approximately 50% risk reduction [odd ratio (OR), 0.51; 95% confidence interval (CI), 0.3–0.8; P = 0.003]. Conversely, the –866G/G genotype was associated with increased risk (OR, 1.31; 95% CI, 1.01–1.71). Overall, the population risk attributable to the UCP2 –866G/G genotype was about 12%. After stratifying for the PPAR2 polymorphism, the increased risk conferred by the UCP2 G/G genotype was still evident among P12/P12 homozygous subjects (n = 801; OR, 1.38; 95% CI, 1.04–1.83), but seemed to disappear among the X12/A12 subjects (i.e. P12/A12 heterozygous or A12/A12 homozygous subjects; n = 137; OR, 0.87; 95% CI, 0.40–1.91). Whether this apparent difference is entirely due to the different number of carriers of the two PPAR2 genotypes is a likely possibility that deserves deeper investigation. In conclusion, in our population, the –866G/A SNP is associated with T2D. Additional studies in larger samples are needed to investigate the possibility of a concomitant effect of modifier genes such as PPAR2.

This article has been cited by other articles:

				Y.-H. Hsu, T. Niu, Y. Song, L. Tinker, L. H. Kuller, and S. Liu Genetic Variants in the UCP2-UCP3 Gene Cluster and Risk of Diabetes in the Women's Health Initiative Observational Study Diabetes, April 1, 2008; 57(4): 1101 - 1107. [Abstract] [Full Text] [PDF]

				E. Chevillotte, M. Giralt, B. Miroux, D. Ricquier, and F. Villarroya Uncoupling Protein-2 Controls Adiponectin Gene Expression in Adipose Tissue Through the Modulation of Reactive Oxygen Species Production Diabetes, April 1, 2007; 56(4): 1042 - 1050. [Abstract] [Full Text] [PDF]

				H. Oberkofler, K. Klein, T. K. Felder, F. Krempler, and W. Patsch Role of Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha} in the Transcriptional Regulation of the Human Uncoupling Protein 2 Gene in INS-1E Cells Endocrinology, February 1, 2006; 147(2): 966 - 976. [Abstract] [Full Text] [PDF]

				X. Yu, D. R. Jacobs Jr, P. J. Schreiner, M. D. Gross, M. W. Steffes, and M. Fornage The Uncoupling Protein 2 Ala55Val Polymorphism Is Associated with Diabetes Mellitus: The CARDIA Study Clin. Chem., August 1, 2005; 51(8): 1451 - 1456. [Abstract] [Full Text] [PDF]