uncoupling protein 2


Gene Symbol: uncoupling protein 2
Description: uncoupling protein 2
Alias: BMIQ4, SLC25A8, UCPH, mitochondrial uncoupling protein 2, solute carrier family 25 member 8, uncoupling protein 2 (mitochondrial, proton carrier)
Species: human
Products:     uncoupling protein 2

Top Publications

  1. Xiu L, Weng J, Sui Y, Wang J, Yan J, Huang Z. [Common variants in beta 3-adrenergic-receptor and uncoupling protein-2 genes are associated with type 2 diabetes and obesity]. Zhonghua Yi Xue Za Zhi. 2004;84:375-9 pubmed
    ..The homozygote of beta(3)-AR gene Trp64Arg mutation is related with diabetes. The accumulation of the effects of two micro-genes creates obvious phenotypic effects. ..
  2. Shen H, Qi L, Tai E, Chew S, Tan C, Ordovas J. Uncoupling protein 2 promoter polymorphism -866G/A, central adiposity, and metabolic syndrome in Asians. Obesity (Silver Spring). 2006;14:656-61 pubmed
    A polymorphism in the promoter region of uncoupling protein 2 gene -866G/A has been associated with its expression levels in adipose tissue, the risk of obesity, and metabolic abnormalities...
  3. Cho Y, Ritchie M, Moore J, Park J, Lee K, Shin H, et al. Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus. Diabetologia. 2004;47:549-554 pubmed publisher
    ..The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor ..
  4. Cha M, Kim I, Kim K, Kang B, Choi S, Yoon Y. Association of UCP2 and UCP3 gene polymorphisms with serum high-density lipoprotein cholesterol among Korean women. Metabolism. 2007;56:806-13 pubmed
    ..09% of the variation in serum HDL cholesterol levels independent of body mass index. We believe that our results may provide clues to the association of UCP genes with the risk of atherosclerosis through their effects on HDL cholesterol. ..
  5. Echtay K, Esteves T, Pakay J, Jekabsons M, Lambert A, Portero Otin M, et al. A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. EMBO J. 2003;22:4103-10 pubmed
    ..Our findings indicate that hydroxynonenal is not merely toxic, but may be a biological signal to induce uncoupling through UCPs and ANT and thus decrease mitochondrial ROS production. ..
  6. Lee Y, Kim W, Yu B, Park B, Kim L, Shin H. Association of the ins/del polymorphisms of uncoupling protein 2 (UCP2) with BMI in a Korean population. Biochem Biophys Res Commun. 2008;371:767-71 pubmed publisher
    ..Our results suggest that subjects with a 45bp insertion allele of UCP2+3474 ins/del might have a higher risk of developing obesity, although the biological effects of this variant are not completely known. ..
  7. Gioli Pereira L, Santos P, Sugaya L, Ferreira N, Krieger J, Pereira A, et al. Association between UCP2 A55V polymorphism and risk of cardiovascular events in patients with multi-vessel coronary arterial disease. BMC Med Genet. 2013;14:40 pubmed publisher
    UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction...
  8. Kovacs P, Ma L, Hanson R, Franks P, Stumvoll M, Bogardus C, et al. Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians. Diabetologia. 2005;48:2292-5 pubmed
    ..Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians. ..
  9. Lindholm E, Klannemark M, Agardh E, Groop L, Agardh C. Putative role of polymorphisms in UCP1-3 genes for diabetic nephropathy. J Diabetes Complications. 2004;18:103-7 pubmed
    ..4+/-4.2 vs. 25.3+/-4.3 kg/m(2); P=.01). We conclude that studied polymorphisms in the UCP1-3 genes do not play a major role in the development of micro- or macroalbuminuria in Scandinavian diabetic patients. ..

More Information


  1. Beitelshees A, Finck B, Leone T, Cresci S, Wu J, Province M, et al. Interaction between the UCP2 -866 G>A polymorphism, diabetes, and beta-blocker use among patients with acute coronary syndromes. Pharmacogenet Genomics. 2010;20:231-8 pubmed publisher
    ..To assess functional correlates of -866G>A, we compared uncoupling protein 2 (UCP2) expression in the skeletal muscle of obese participants by genotype and compared the activity of ..
  2. Yu X, Wieczorek S, Franke A, Yin H, Pierer M, Sina C, et al. Association of UCP2 -866 G/A polymorphism with chronic inflammatory diseases. Genes Immun. 2009;10:601-5 pubmed publisher
    ..82-0.95), P=0.0008), with the -866A allele associated with a decreased risk to diseases. As the -866A allele increases gene expression, our findings suggest a protective role of the UCP2 protein in chronic inflammatory diseases...
  3. Andersen G, Dalgaard L, Justesen J, Anthonsen S, Nielsen T, Thørner L, et al. The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17?636 Danes. Int J Obes (Lond). 2013;37:175-81 pubmed publisher
    b>Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in ?-cells...
  4. Damcott C, Feingold E, Moffett S, Barmada M, Marshall J, Hamman R, et al. Genetic variation in uncoupling protein 3 is associated with dietary intake and body composition in females. Metabolism. 2004;53:458-64 pubmed
    ..The lean mass model showed no statistically significant association with either UCP3 variant. These results support a role for UCP3 in fuel substrate management and energy metabolism, which may influence body weight regulation. ..
  5. Derdak Z, Mark N, Beldi G, Robson S, Wands J, BAFFY G. The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res. 2008;68:2813-9 pubmed publisher
    ..These findings link UCP2 with molecular mechanisms of chemoresistance. Targeting UCP2 may be considered a novel treatment strategy for cancer. ..
  6. Jia J, Zhang X, Ge C, Jois M. The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes. Obes Rev. 2009;10:519-26 pubmed publisher
    ..This review summarizes data supporting the roles of UCP2 and UCP3 in energy dissipation, as well as the genetic variety association with fat metabolism, obesity and diabetes in humans. ..
  7. Berentzen T, Dalgaard L, Petersen L, Pedersen O, Sørensen T. Interactions between physical activity and variants of the genes encoding uncoupling proteins -2 and -3 in relation to body weight changes during a 10-y follow-up. Int J Obes (Lond). 2005;29:93-9 pubmed
    ..This study does not support that interactions between physical activity and variants in the UCP2- or UCP3-gene are major determinants of subsequent weight changes in Danish Caucasian men. ..
  8. Hsu Y, Niu T, Song Y, Tinker L, Kuller L, Liu S. Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study. Diabetes. 2008;57:1101-7 pubmed publisher
    ..These data warrant further confirmation in future prospective and experimental studies. ..
  9. Rousset S, Mozo J, Dujardin G, Emre Y, Masscheleyn S, Ricquier D, et al. UCP2 is a mitochondrial transporter with an unusual very short half-life. FEBS Lett. 2007;581:479-82 pubmed
    This study focused on the stability of UCP2 (uncoupling protein 2), a mitochondrial carrier located in the inner membrane of mitochondrion...
  10. Akrami S, Heidari J, Heshmat R, Amiri P, Fakhrzadeh H, Pajouhi M. The common -866G/A polymorphism of the UCP2 gene in healthy Iranians compared with world populations. Hum Biol. 2007;79:103-10 pubmed
    b>Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily. It is proposed as a candidate gene for obesity...
  11. Brown J, Thomas S, Digby J, Dunmore S. Glucose induces and leptin decreases expression of uncoupling protein-2 mRNA in human islets. FEBS Lett. 2002;513:189-92 pubmed
    ..This is the first report of UCP-2 expression in human islets and provides novel evidence of its role in the loss of beta-cell function in diabetes. ..
  12. Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi Meyrueis C, et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet. 1997;15:269-72 pubmed
    ..Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli. ..
  13. Duarte N, Colagiuri S, Palu T, Wang X, Wilcken D. A 45-bp insertion/deletion polymorphism of uncoupling protein 2 in relation to obesity in Tongans. Obes Res. 2003;11:512-7 pubmed
    ..This may be the result of a founder effect and may be relevant to the prevalence of obesity and type 2 diabetes in Tonga. ..
  14. Rance K, Johnstone A, Murison S, Duncan J, Wood S, Speakman J. Plasma leptin levels are related to body composition, sex, insulin levels and the A55V polymorphism of the UCP2 gene. Int J Obes (Lond). 2007;31:1311-8 pubmed
    ..119) or Log(e) insulin (P=0.252). These data suggest that the A55V polymorphism directly affected the levels of leptin but not via an effect on insulin. ..
  15. Sasahara M, Nishi M, Kawashima H, Ueda K, Sakagashira S, Furuta H, et al. Uncoupling protein 2 promoter polymorphism -866G/A affects its expression in beta-cells and modulates clinical profiles of Japanese type 2 diabetic patients. Diabetes. 2004;53:482-5 pubmed
    Common uncoupling protein 2 (UCP2) promoter polymorphism -866G/A is reported to be associated with its expression in adipose tissue and the risk of obesity in Caucasians...
  16. Dhamrait S, Stephens J, Cooper J, Acharya J, Mani A, Moore K, et al. Cardiovascular risk in healthy men and markers of oxidative stress in diabetic men are associated with common variation in the gene for uncoupling protein 2. Eur Heart J. 2004;25:468-75 pubmed
    Oxidative stress reduces total antioxidant status (TAOS) and is implicated in atherogenesis. Mitochondrial uncoupling protein 2 (UCP2) negatively regulates reactive oxygen species generation...
  17. Mancini F, Sabatino L, Colantuoni V, Pasanisi F, Finelli C, Contaldo F, et al. Variants of uncoupling protein-2 gene and obesity: interaction with peroxisome proliferator-activated receptorgamma2. Clin Endocrinol (Oxf). 2003;59:817-22 pubmed
    ..This negative finding is not modified after a combined analysis of the UCP2 polymorphism and the Pro12Ala polymorphism of PPARgamma2. ..
  18. Vimaleswaran K, Radha V, Ghosh S, Majumder P, Sathyanarayana Rao M, Mohan V. Uncoupling protein 2 and 3 gene polymorphisms and their association with type 2 diabetes in asian indians. Diabetes Technol Ther. 2011;13:19-25 pubmed publisher
    ..Ala55Val and -55C/T polymorphisms at the UCP3-2 loci are associated with a significantly reduced risk of developing type 2 diabetes in Asian Indians. ..
  19. Ricquier D, Bouillaud F. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J. 2000;345 Pt 2:161-79 pubmed
    ..Other aims will be to investigate the possible roles of UCP2 and UCP3 in response to oxidative stress, lipid peroxidation, inflammatory processes, fever and regulation of temperature in certain specific parts of the body. ..
  20. D Adamo M, Perego L, Cardellini M, Marini M, Frontoni S, Andreozzi F, et al. The -866A/A genotype in the promoter of the human uncoupling protein 2 gene is associated with insulin resistance and increased risk of type 2 diabetes. Diabetes. 2004;53:1905-10 pubmed
    ..84, 95% CI 1.03-3.28; P = 0.037), but not in men. These results indicate that the -866A/A genotype of the UCP2 gene may contribute to diabetes susceptibility by affecting insulin sensitivity. ..
  21. Chen H, Lee W, Wang W, Huang M, Lee Y, Pan W. Ala55Val polymorphism on UCP2 gene predicts greater weight loss in morbidly obese patients undergoing gastric banding. Obes Surg. 2007;17:926-33 pubmed
    ..05). Ala55Val may play a crucial role in obesity development and weight loss after LAGB. It may be considered as clinicians incorporate genetic susceptibility testing into weight loss prediction prior to bariatric operations. ..
  22. Schäuble N, Geller F, Siegfried W, Goldschmidt H, Remschmidt H, Hinney A, et al. No evidence for involvement of the promoter polymorphism -866 G/A of the UCP2 gene in childhood-onset obesity in humans. Exp Clin Endocrinol Diabetes. 2003;111:73-6 pubmed
    ..Allele and genotype frequencies did not differ between the extremely obese and never-obese subjects. In conclusion, we cannot confirm the results of ) in our young sample. ..
  23. Rudofsky G, Schroedter A, Schlotterer A, Voron ko O, Schlimme M, Tafel J, et al. Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with type 1 diabetes. Diabetes Care. 2006;29:89-94 pubmed
    ..Thus, the results presented here support the hypothesis that higher expression of uncoupling protein might prevent mitochondria-mediated neuronal injury and, ultimately, diabetic neuropathy. ..
  24. Boss O, Samec S, Paoloni Giacobino A, Rossier C, Dulloo A, Seydoux J, et al. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett. 1997;408:39-42 pubmed
    ..This new member of the UCP family is a candidate protein for the modulation of the respiratory control in skeletal muscle. ..
  25. Wang T, Huang M, Lin H, Hsiang C, Ko A, Chang W, et al. UCP2 A55V variant is associated with obesity and related phenotypes in an aboriginal community in Taiwan. Int J Obes (Lond). 2007;31:1746-52 pubmed
    ..5% of obese disorders and increase insulin concentrations. The V-A-T haplotype within UCP2-UCP3 gene cluster is also significantly associated with obesity in Paiwan aborigines. ..
  26. Crispim D, Fagundes N, dos Santos K, Rheinheimer J, Bouças A, de Souza B, et al. Polymorphisms of the UCP2 gene are associated with proliferative diabetic retinopathy in patients with diabetes mellitus. Clin Endocrinol (Oxf). 2010;72:612-9 pubmed publisher
    b>Uncoupling protein 2 (UCP2) plays a role in controlling reactive oxygen species (ROS) production by mitochondria...
  27. de Souza B, Assmann T, Kliemann L, Marcon A, Gross J, Canani L, et al. The presence of the -866A/55Val/Ins haplotype in the uncoupling protein 2 (UCP2) gene is associated with decreased UCP2 gene expression in human retina. Exp Eye Res. 2012;94:49-55 pubmed publisher
    b>Uncoupling protein 2 (UCP2) is a mitochondrial transporter present in the inner membrane of mitochondria, and it uncouples substrate oxidation from ATP synthesis, thereby dissipating the membrane potential energy and consequently ..
  28. Oktavianthi S, Trimarsanto H, Febinia C, Suastika K, Saraswati M, Dwipayana P, et al. Uncoupling protein 2 gene polymorphisms are associated with obesity. Cardiovasc Diabetol. 2012;11:41 pubmed publisher
    b>Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM)...
  29. Bulotta A, Ludovico O, Coco A, Di Paola R, Quattrone A, Carella M, et al. 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. J Clin Endocrinol Metab. 2005;90:1176-80 pubmed
    ..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 PPAR gamma 2. ..
  30. Vogler S, Goedde R, Miterski B, Gold R, Kroner A, Koczan D, et al. Association of a common polymorphism in the promoter of UCP2 with susceptibility to multiple sclerosis. J Mol Med (Berl). 2005;83:806-11 pubmed
    b>Uncoupling protein 2 (UCP2) is a member of the mitochondrial proton transport family that uncouples proton entry to the mitochondria from ATP synthesis. UCP2 expression levels have been linked to predisposition to diabetes and obesity...
  31. Flachs P, Sponarova J, Kopecky P, Horvath O, Sediva A, Nibbelink M, et al. Mitochondrial uncoupling protein 2 gene transcript levels are elevated in maturating erythroid cells. FEBS Lett. 2007;581:1093-7 pubmed
    b>Mitochondrial uncoupling protein 2 (UCP2) is abundant in developing monocyte/macrophage cells and may affect hematopoiesis by reducing formation of reactive oxygen species...
  32. Kosuge K, Soma M, Nakayama T, Aoi N, Sato M, Haketa A, et al. Human uncoupling protein 2 and 3 genes are associated with obesity in Japanese. Endocrine. 2008;34:87-95 pubmed publisher
    ..042) in the overall distribution of the haplotype (UCP3 rs2075577, UCP2 rs660339). Nonsynonymous rs660339 in the human UCP2 gene in men, and the haplotype (UCP3 rs2075577-UCP2 rs660339) in women might be good obesity markers. ..
  33. Bielinski S, Pankow J, Boerwinkle E, Bray M, Kao W, Folsom A. Lack of association between uncoupling protein-2 Ala55Val polymorphism and incident diabetes in the atherosclerosis risk in communities study. Acta Diabetol. 2008;45:179-82 pubmed publisher
    ..The Ala55Val polymorphism of UCP2 was not associated with incident T2DM in the ARIC cohort. ..
  34. Yoon Y, Park B, Cha M, Kim K, Cheong H, Choi Y, et al. Effects of genetic polymorphisms of UCP2 and UCP3 on very low calorie diet-induced body fat reduction in Korean female subjects. Biochem Biophys Res Commun. 2007;359:451-6 pubmed
    ..002 and 0.004; P(corr)=0.03 and 0.01, respectively), and these results suggested that UCP2-3 polymorphisms were important genetic factor for the VLCD-induced reduction of body fat mass. ..
  35. Mottagui Tabar S, Hoffstedt J, Brookes A, Jiao H, Arner P, Dahlman I. Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity. Horm Res. 2008;69:31-6 pubmed
    ..013 and 0.048, respectively). UCP1 and UCP2 showed no association with insulin sensitivity. Polymorphisms in ADRB1 and UCP3 may contribute to insulin resistance rather than obesity among Swedish women. ..
  36. Franco Hincapié L, Duque C, Parra M, Gallego N, Villegas A, Ruiz Linares A, et al. [Association between polymorphism in uncoupling proteins and type 2 diabetes in a northwestern Colombian population]. Biomedica. 2009;29:108-18 pubmed
    ..These associations remained after adjustment using individual genetic admixture estimates. Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population. ..
  37. Gable D, Stephens J, Cooper J, Miller G, Humphries S. Variation in the UCP2-UCP3 gene cluster predicts the development of type 2 diabetes in healthy middle-aged men. Diabetes. 2006;55:1504-11 pubmed
    ..Both effects are exacerbated by obesity. ..
  38. Jun H, Kim I, Lee H, Kang J, Kim J, Shin H, et al. Effects of UCP2 and UCP3 variants on the manifestation of overweight in Korean children. Obesity (Silver Spring). 2009;17:355-62 pubmed publisher
    ..6 +/- 2.3 kg/m(2) vs. 16.1 +/- 1.9 kg/m(2), P = 0.016). Low physical activity may aggravate the susceptibility to overweight in UCP2-866GG and UCP3-55CC carriers. ..
  39. Heidari J, Akrami S, Heshmat R, Amiri P, Fakhrzadeh H, Pajouhi M. Association study of the -866G/A UCP2 gene promoter polymorphism with type 2 diabetes and obesity in a Tehran population: a case control study. Arch Iran Med. 2010;13:384-90 pubmed publisher
    A functional polymorphism in the uncoupling protein 2 (UCP2) gene promoter has been associated with obesity and type 2 diabetes (T2D) in some populations. The impact of UCP2 polymorphisms on diabetes and obesity is still under debate...
  40. Le Fur S, Le Stunff C, Dos Santos C, Bougneres P. The common -866 G/A polymorphism in the promoter of uncoupling protein 2 is associated with increased carbohydrate and decreased lipid oxidation in juvenile obesity. Diabetes. 2004;53:235-9 pubmed
    ..6 +/- 1.2) of calories derived from carbohydrates to those from lipids compared with G/A or G/G obese children (1.4 +/- 0.2, P = 0.003), suggesting a role for UCP2 in the partitioning of metabolic fuels. ..
  41. Ji Q, Ikegami H, Fujisawa T, Kawabata Y, Ono M, Nishino M, et al. A common polymorphism of uncoupling protein 2 gene is associated with hypertension. J Hypertens. 2004;22:97-102 pubmed
    ..A functional polymorphism in the uncoupling protein 2 (UCP2) promoter has been reported to be associated with obesity in Caucasians...
  42. Reis A, Dubois Laforgue D, Bellanne Chantelot C, Timsit J, Velho G. A polymorphism in the promoter of UCP2 gene modulates lipid levels in patients with type 2 diabetes. Mol Genet Metab. 2004;82:339-44 pubmed
    ..The implications of this effect in the evolution of type 2 diabetes and its macrovascular complications deserve to be investigated. ..
  43. Martinez Hervas S, Mansego M, de Marco G, Martinez F, Alonso M, Morcillo S, et al. Polymorphisms of the UCP2 gene are associated with body fat distribution and risk of abdominal obesity in Spanish population. Eur J Clin Invest. 2012;42:171-8 pubmed publisher
    ..Polymorphisms of the UCP2 gene (rs660339 and rs659366) were associated with central obesity. This study shows association between the UCP2 gene and the susceptibility to obesity and body fat distribution in a south European population. ..
  44. Ochoa M, Santos J, Azcona C, Moreno Aliaga M, Martinez Gonzalez M, Martinez J, et al. Association between obesity and insulin resistance with UCP2-UCP3 gene variants in Spanish children and adolescents. Mol Genet Metab. 2007;92:351-8 pubmed
    ..Thus, the (-866A; rs659366)-(Ins; 45bp)-(-55C; rs1800849) haplotype may protect against insulin resistance in the obese population group. ..
  45. Oberkofler H, Iglseder B, Klein K, Unger J, Haltmayer M, Krempler F, et al. Associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol. 2005;25:604-10 pubmed
    Reactive oxygen species (ROS) contribute to atherogenesis. Uncoupling protein 2 (UCP2) reduces mitochondrial ROS generation and protects against the disease in animal models...
  46. Lee K, Lee I, Han J, Song D, Kim Y, Song H, et al. Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis. Circ Res. 2005;96:1200-7 pubmed
    ..b>Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production...
  47. Yu X, Jacobs D, Schreiner P, Gross M, Steffes M, Fornage M. The uncoupling protein 2 Ala55Val polymorphism is associated with diabetes mellitus: the CARDIA study. Clin Chem. 2005;51:1451-6 pubmed
    ..The VV genotype of the UCP2 polymorphism was positively related to diabetes. It may involve increased insulin resistance in those with impaired glucose homeostasis. ..
  48. Vidal Puig A, Solanes G, Grujic D, Flier J, Lowell B. UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun. 1997;235:79-82 pubmed
    ..Since UCP3 is minimally expressed in human heart and other critical organs, it is a promising target for anti-obesity drug development aimed at increasing thermogenesis. ..
  49. Vozza A, Parisi G, De Leonardis F, Lasorsa F, Castegna A, Amorese D, et al. UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proc Natl Acad Sci U S A. 2014;111:960-5 pubmed publisher
    b>Uncoupling protein 2 (UCP2) is involved in various physiological and pathological processes such as insulin secretion, stem cell differentiation, cancer, and aging. However, its biochemical and physiological function is still under debate...
  50. Dalgaard L, Andersen G, Larsen L, Sørensen T, Andersen T, Drivsholm T, et al. Mutational analysis of the UCP2 core promoter and relationships of variants with obesity. Obes Res. 2003;11:1420-7 pubmed
    To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain...
  51. Xu K, Zhang M, Cui D, Fu Y, Qian L, Gu R, et al. UCP2 -866G/A and Ala55Val, and UCP3 -55C/T polymorphisms in association with type 2 diabetes susceptibility: a meta-analysis study. Diabetologia. 2011;54:2315-24 pubmed publisher
    ..This conclusion warrants confirmation by further studies. ..
  52. Lapice E, Pinelli M, Pisu E, Monticelli A, Gambino R, Pagano G, et al. Uncoupling protein 2 G(-866)A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients. Cardiovasc Diabetol. 2010;9:68 pubmed publisher
    This study evaluated the relationship between the G(-866)A polymorphism of the uncoupling protein 2 (UCP2) gene and high-sensitivity C reactive protein (hs-CRP) plasma levels in diabetic patients...
  53. Esterbauer H, Schneitler C, Oberkofler H, Ebenbichler C, Paulweber B, Sandhofer F, et al. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nat Genet. 2001;28:178-83 pubmed
    ..Despite its modest effect, but because of its high frequency (approximately 63%), the more-common risk allele conferred a relatively large population-attributable risk accounting for 15% of the obesity in the population studied. ..
  54. Liu X, Zhang B, Liu X, Shen Y, Li J, Zhao N, et al. A 45-bp insertion/deletion polymorphism in uncoupling protein 2 is not associated with obesity in a Chinese population. Biochem Genet. 2012;50:784-96 pubmed publisher
    The association of a 45-bp insertion/deletion (UCP2-45 bp I/D) polymorphism in uncoupling protein 2 with body mass index (BMI) remains controversial. A case-control study was conducted to examine the association in a Chinese population...
  55. Santandreu F, Roca P, Oliver J. Uncoupling protein-2 knockdown mediates the cytotoxic effects of cisplatin. Free Radic Biol Med. 2010;49:658-66 pubmed publisher
    ..In conclusion, we show for the first time that UCP2 knockdown participates in the mechanism of action of cisplatin, thus providing evidence that targeting UCP2 may offer clinical benefit in the treatment of cancer. ..
  56. Pfefferle A, Mailloux R, Adjeitey C, Harper M. Glutathionylation of UCP2 sensitizes drug resistant leukemia cells to chemotherapeutics. Biochim Biophys Acta. 2013;1833:80-9 pubmed publisher
    ..In contrast, diamide had very little effect on proton leak in HL-60 cells. Collectively, our observations indicate that manipulation of UCP2 glutathionylation status can serve as a therapeutic strategy for cancer treatment...
  57. Sesti G, Cardellini M, Marini M, Frontoni S, D Adamo M, Del Guerra S, et al. A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. Diabetes. 2003;52:1280-3 pubmed
    ..These results indicate that the common -866G/A polymorphism in the UCP2 gene may contribute to the biological variation of insulin secretion in humans. ..
  58. Salpea K, Talmud P, Cooper J, Maubaret C, Stephens J, Abelak K, et al. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis. 2010;209:42-50 pubmed publisher
    ..The association of the UCP2 functional promoter variant with the LTL implies a link between mitochondrial production of reactive oxygen species and shorter telomere length in T2D. ..
  59. Yang M, Huang Q, Wu J, Yin J, Sun H, Liu H, et al. Effects of UCP2 -866 G/A and ADRB3 Trp64Arg on rosiglitazone response in Chinese patients with Type 2 diabetes. Br J Clin Pharmacol. 2009;68:14-22 pubmed publisher
    ..12 mmol l(-1), P < 0.05) (1.68, 4.08 vs.-9.18, 11.40) compared with ADRB3 Trp64Trp. UCP2 -866 G/A and ADRB3 Trp64Arg polymorphisms are associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese T2DM patients. ..
  60. Labayen I, Ortega F, Sjostrom M, Nilsson T, Olsson L, Ruiz J. Association of common variants of UCP2 gene with low-grade inflammation in Swedish children and adolescents; the European Youth Heart Study. Pediatr Res. 2009;66:350-4 pubmed publisher
    ..Given the implication of complement factors on atherosclerosis process, these results contribute to explain the reduced cardiovascular risk associated with the A allele of the UCP2 -866G>A polymorphism. ..
  61. Trenker M, Malli R, Fertschai I, Levak Frank S, Graier W. Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport. Nat Cell Biol. 2007;9:445-452 pubmed publisher
    ..Moreover, the identification of proteins fundemental for mitochondrial Ca(2+) uptake expands our knowledge of the physiological role for mitochondrial Ca(2+) sequestration. ..
  62. Teshima Y, Akao M, Jones S, Marban E. Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes. Circ Res. 2003;93:192-200 pubmed
    ..Thus, overexpression of UCP2 attenuates ROS generation and prevents mitochondrial Ca2+ overload, revealing a novel mechanism of cardioprotection. ..
  63. Kim H, Park K, Koo T, Huh S, Lee I. The modulating effects of the overexpression of uncoupling protein 2 on the formation of reactive oxygen species in vascular cells. Diabetes Res Clin Pract. 2007;77 Suppl 1:S46-8 pubmed
    b>Uncoupling protein 2 (UCP-2) is a newly identified member of the mitochondrial anion carrier family and shares 60% sequence identity with the well-characterized thermogenic UCP-1 from brown adipose tissue...
  64. Cheurfa N, Dubois Laforgue D, Ferrarezi D, Reis A, Brenner G, Bouche C, et al. The common -866G>A variant in the promoter of UCP2 is associated with decreased risk of coronary artery disease in type 2 diabetic men. Diabetes. 2008;57:1063-8 pubmed publisher
    b>Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall...
  65. Qian L, Xu K, Xu X, Gu R, Liu X, Shan S, et al. UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms in association with obesity susceptibility - a meta-analysis study. PLoS ONE. 2013;8:e58939 pubmed publisher
    ..And our results did not support the association between UCP2 Ala55Val, UCP3 -55C/T polymorphisms and obesity in the populations investigated. This conclusion warrants confirmation by further studies. ..
  66. Papazoglou D, Papathanasiou P, Papanas N, Papatheodorou K, Chatziangeli E, Nikitidis I, et al. Uncoupling protein-2 45-base pair insertion/deletion polymorphism: is there an association with severe obesity and weight loss in morbidly obese subjects?. Metab Syndr Relat Disord. 2012;10:307-11 pubmed publisher
    ..048). There is no association of the UCP2 ins/del polymorphism with morbid obesity in our population, but this genotype appears to be linked with a favorable response to dietary changes in metabolically healthy obese subjects. ..
  67. Stephens J, Dhamrait S, Mani A, Acharya J, Moore K, Hurel S, et al. Interaction between the uncoupling protein 2 -866G>A gene variant and cigarette smoking to increase oxidative stress in subjects with diabetes. Nutr Metab Cardiovasc Dis. 2008;18:7-14 pubmed
    ..5% vs. 51.4+/-9.5%, p=0.04; F(2)-isoprostanes 1133.6+/-701.2 pg ml(-1) vs. 500.8+/-64.7 pg ml(-1), p=0.04). This study demonstrates an interaction between the UCP2 -866G>A variant and smoking to increase oxidative stress in vivo. ..
  68. Echtay K, Roussel D, St Pierre J, Jekabsons M, Cadenas S, Stuart J, et al. Superoxide activates mitochondrial uncoupling proteins. Nature. 2002;415:96-9 pubmed
    ..Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria. ..
  69. Rosmond R, Bouchard C, Bjorntorp P. Lack of association between the uncoupling protein-2 Ala55Val gene polymorphism and phenotypic features of the Metabolic Syndrome. Biochim Biophys Acta. 2002;1588:103-5 pubmed
    ..From these data, we conclude that the C-->T substitution in exon 4 of the UCP2 gene does not contribute to the predisposition to be affected by the Metabolic Syndrome. ..
  70. Qin L, Wen J, Qu Y, Huang Q. Lack of association of functional UCP2 -866G/A and Ala55Val polymorphisms and type 2 diabetes in the Chinese population based on a case-control study and a meta-analysis. Genet Mol Res. 2013;12:3324-34 pubmed publisher
    b>Uncoupling protein 2 (UCP2) is a mitochondrial transporter protein and can affect the function of ?-cells...
  71. Krempler F, Esterbauer H, Weitgasser R, Ebenbichler C, Patsch J, Miller K, et al. A functional polymorphism in the promoter of UCP2 enhances obesity risk but reduces type 2 diabetes risk in obese middle-aged humans. Diabetes. 2002;51:3331-5 pubmed
    ..We previously observed an association of a functional G/A polymorphism in the uncoupling protein 2 (UCP2) promoter with obesity...
  72. Hamada T, Kotani K, Fujiwara S, Sano Y, Domichi M, Tsuzaki K, et al. The UCP2-866 A/A genotype is associated with low density lipoprotein particle sizes in the general population. Med Sci Monit. 2008;14:CR107-11 pubmed
    ..012). The -866 A/A genotype may contribute to reduced LDL particle size levels, a significant risk factor for the development of coronary artery disease. ..
  73. Samudio I, Fiegl M, McQueen T, Clise Dwyer K, Andreeff M. The warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein 2 activation. Cancer Res. 2008;68:5198-205 pubmed publisher
    ..was mediated by mitochondrial uncoupling in leukemia cells and was accompanied by increased expression of uncoupling protein 2 (UCP2)...
  74. Lee H, Ryu H, Shin H, Park B, Kim J, Cho Y, et al. Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM. Clin Chim Acta. 2008;398:27-33 pubmed publisher
    ..38, 95% CI=1.03-1.85). This association was more obvious in women (P=0.022, OR=1.58, 95% CI=1.07-2.34). Our results suggest that the UCP2 -5331G>A and UCP3 -2078C>T polymorphisms are susceptibility markers for T2DM among Koreans. ..
  75. Hsiao T, Wu L, Hwang Y, Huang S, Lin E. Effect of the common -866G/A polymorphism of the uncoupling protein 2 gene on weight loss and body composition under sibutramine therapy in an obese Taiwanese population. Mol Diagn Ther. 2010;14:101-6 pubmed publisher
    ..In this study, our goal was to investigate whether a common SNP, -866G/A (rs659366), in the uncoupling protein 2 (UCP2) gene could influence weight reduction and body composition under sibutramine therapy in an obese ..
  76. Srivastava N, Prakash J, Lakhan R, Agarwal C, Pant D, Mittal B. A common polymorphism in the promoter of UCP2 is associated with obesity and hyperinsulenemia in northern Indians. Mol Cell Biochem. 2010;337:293-8 pubmed publisher
    A polymorphism in the promoter region of uncoupling protein 2 gene -866 G/A has been associated with its expression levels, the risk of obesity, and metabolic abnormalities...
  77. Hurtaud C, Gelly C, Bouillaud F, Levi Meyrueis C. Translation control of UCP2 synthesis by the upstream open reading frame. Cell Mol Life Sci. 2006;63:1780-9 pubmed
    b>Uncoupling protein 2 (UCP2) belongs to a family of transporters of the mitochondrial inner membrane...
  78. Humphries S, Cooper J, Talmud P, Miller G. Candidate gene genotypes, along with conventional risk factor assessment, improve estimation of coronary heart disease risk in healthy UK men. Clin Chem. 2007;53:8-16 pubmed
    ..Of the 12 genes previously associated with CHD risk, in stepwise multivariate risk analysis, uncoupling protein 2 (UCP2; P = 0.0001), apolipoprotein E (APOE; P = 0.0003), lipoprotein lipase (LPL; P = 0...
  79. Oğuzkan Balci S, Col Araz N, Nacak M, Araz M, Sabanci H, Balat A, et al. Mitochondrial uncoupling protein 2 (UCP2) gene polymorphisms are associated with childhood obesity and related metabolic disorders. J Pediatr Endocrinol Metab. 2013;26:277-83 pubmed publisher
    This study aimed to investigate the possible role of uncoupling protein 2 (UCP2) gene polymorphisms in childhood obesity and related metabolic disorders...
  80. Horimoto M, Resnick M, Konkin T, Routhier J, Wands J, BAFFY G. Expression of uncoupling protein-2 in human colon cancer. Clin Cancer Res. 2004;10:6203-7 pubmed
    ..These findings may foster the idea that UCP2 is part of a novel adaptive response by which oxidative stress is modulated in colon cancer. ..
  81. Wang H, Chu W, Lu T, Hasstedt S, Kern P, Elbein S. Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion. Am J Physiol Endocrinol Metab. 2004;286:E1-7 pubmed
    ..However, the associated allele and the effects on gene expression are opposite to those reported previously. ..