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

被引：33

作者：

Andersen, G. ^{[1
]}

Dalgaard, L. T. ^{[2
]}

Justesen, J. M. ^{[3
]}

Anthonsen, S. ^{[1
,2
]}

Nielsen, T. ^{[3
]}

Thorner, L. W. ^{[1
]}

Witte, D. ^{[4
]}

Jorgensen, T. ^{[5
,6
]}

Clausen, J. O. ^{[4
]}

Lauritzen, T. ^{[7
]}

Holmkvist, J. ^{[1
]}

Hansen, T. ^{[1
,3
,8
]}

Pedersen, O. ^{[1
,3
,6
,9
]}

机构：

[1] Hagedorn Res Inst, Gentofte, Denmark

[2] Roskilde Univ, Dept Sci Syst & Models, DK-4000 Roskilde, Denmark

[3] Univ Copenhagen, Fac Hlth Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[4] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[5] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark

[6] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark

[7] Univ Aarhus, Dept Gen Practice, Aarhus, Denmark

[8] Univ So Denmark, Fac Hlth Sci, Odense, Denmark

[9] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark

来源：

INTERNATIONAL JOURNAL OF OBESITY | 2013年 / 37卷 / 02期

基金：

英国医学研究理事会;

关键词：

diabetes; insulin sensitivity; genetics; uncoupling protein 2; -866G/A polymorphism; rs659366; UNCOUPLING PROTEIN-2 GENE; COMMON POLYMORPHISM; UCP2; GENE; PROMOTER POLYMORPHISM; OXIDATIVE STRESS; REDUCED RISK; VARIANTS; SECRETION; EXPRESSION; HEALTH;

D O I：

10.1038/ijo.2012.22

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

CONTEXT: Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in beta-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus. OBJECTIVE: To determine the influence of a functional UCP2 promoter polymorphism (-866G-A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes. DESIGN: We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations. RESULTS: We found no consistent associations between the UCP2 -866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12 984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15 107 individuals showed no association. The -866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05). CONCLUSIONS: The UCP2 -866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis. International Journal of Obesity (2013) 37, 175-181; doi:10.1038/ijo.2012.22; published online 21 February 2012

引用

页码：175 / 181

页数：7

共 60 条

[1]

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes [J].

Andersen, G ;

Overgaard, J ;

Albrechtsen, A ;

Glümer, C ;

Borch-Johnsen, K ;

Jorgensen, T ;

Hansen, T ;

Pedersen, O .

DIABETOLOGIA, 2006, 49 (01) :75-82

[2]

Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits [J].

Andreasen, Camilla Helene ;

Mogensen, Mette Sloth ;

Borch-Johnsen, Knut ;

Sandbaek, Annelli ;

Lauritzen, Torsten ;

Almind, Katrine ;

Hansen, Lars ;

Jorgensen, Torben ;

Pedersen, Oluf ;

Hansen, Torben .

BMC MEDICAL GENETICS, 2008, 9

[3]

Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production [J].

Arsenijevic, D ;

Onuma, H ;

Pecqueur, C ;

Raimbault, S ;

Manning, BS ;

Miroux, B ;

Couplan, E ;

Alves-Guerra, MC ;

Goubern, M ;

Surwit, R ;

Bouillaud, F ;

Richard, D ;

Collins, S ;

Ricquier, D .

NATURE GENETICS, 2000, 26 (04) :435-439

[4]

Interaction between the UCP2-866 G>A polymorphism, diabetes, and β-blocker use among patients with acute coronary syndromes [J].

Beitelshees, Amber L. ;

Finck, Brian N. ;

Leone, Teresa C. ;

Cresci, Sharon ;

Wu, Jun ;

Province, Michael A. ;

Fabbrini, Elisa ;

Kirk, Erik ;

Zineh, Issam ;

Klein, Samuel ;

Spertus, John A. ;

Kelly, Daniel P. .

PHARMACOGENETICS AND GENOMICS, 2010, 20 (04) :231-238

[5]

Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3 [J].

Brand, MD ;

Esteves, TC .

CELL METABOLISM, 2005, 2 (02) :85-93

[6]

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].

Bulotta, A ;

Ludovico, O ;

Coco, A ;

Di Paola, R ;

Quattrone, A ;

Carella, M ;

Pellegrini, F ;

Prudente, S ;

Trischitta, V .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (02) :1176-1180

[7]

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[8]

Association of UCP2 and UCP3 gene polymorphisms with serum high-density lipoprotein cholesterol among Korean women [J].

Cha, Min Ho ;

Kim, Il Chul ;

Kim, Kil Soo ;

Kang, Byoung Kab ;

Choi, Sun Mi ;

Yoon, Yoosik .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2007, 56 (06) :806-813

[9]

Uncoupling Proteins: Role in Insulin Resistance and Insulin Insufficiency [J].

Chan, Catherine B. ;

Harper, Mary-Ellen .

CURRENT DIABETES REVIEWS, 2006, 2 (03) :271-283

[10]

Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets [J].

Chan, CB ;

MacDonald, PE ;

Saleh, MC ;

Johns, DC ;

Marbàn, E ;

Wheeler, MB .

DIABETES, 1999, 48 (07) :1482-1486

← 1 2 3 4 5 6 →

The frequent UCP2-866G&gt;A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17 636 Danes

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