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

Louise Torp Dalgaard, Gitte Andersen, Johanne Marie Justesen, Stine Anthonsen, Trine Nielsen, Lise Wegner Thørner, Daniel Witte, Torben Jørgensen, Jesper Clausen, Torsten Lauritzen, Johan Holmkvist, Torben Hansen, Oluf Pedersen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Context: Uncoupling protein 2 (UCP2) is involved in regulating ATP-synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in β-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 analyzed within separate study populations.
    Results: We found no consistent associations between the UCP2 -866 G-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 OR(95% 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 -866 G-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 (IVGTT) in young Caucasian subjects (n=377) was decreased in carriers of the GG-genotype (P=0.05). Conclusions: The UCP2 -866 G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.
    OriginalsprogEngelsk
    TidsskriftInternational Journal of Obesity
    Vol/bind37
    Udgave nummer2
    Sider (fra-til)1775-181
    ISSN0307-0565
    DOI
    StatusUdgivet - 21 feb. 2013

    Citer dette

    Dalgaard, Louise Torp ; Andersen, Gitte ; Justesen, Johanne Marie ; Anthonsen, Stine ; Nielsen, Trine ; Thørner, Lise Wegner ; Witte, Daniel ; Jørgensen, Torben ; Clausen, Jesper ; Lauritzen, Torsten ; Holmkvist, Johan ; Hansen, Torben ; Pedersen, Oluf. / 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. I: International Journal of Obesity. 2013 ; Bind 37, Nr. 2. s. 1775-181.
    @article{a7107424bee746b08caa9875b1ece946,
    title = "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",
    abstract = "Context: Uncoupling protein 2 (UCP2) is involved in regulating ATP-synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in β-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 analyzed within separate study populations. Results: We found no consistent associations between the UCP2 -866 G-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 OR(95{\%} 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 -866 G-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 (IVGTT) in young Caucasian subjects (n=377) was decreased in carriers of the GG-genotype (P=0.05). Conclusions: The UCP2 -866 G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.",
    keywords = "UCP2, Obesity, genetics, insulin resistance",
    author = "Dalgaard, {Louise Torp} and Gitte Andersen and Justesen, {Johanne Marie} and Stine Anthonsen and Trine Nielsen and Th{\o}rner, {Lise Wegner} and Daniel Witte and Torben J{\o}rgensen and Jesper Clausen and Torsten Lauritzen and Johan Holmkvist and Torben Hansen and Oluf Pedersen",
    year = "2013",
    month = "2",
    day = "21",
    doi = "10.1038/ijo.2012.22",
    language = "English",
    volume = "37",
    pages = "1775--181",
    journal = "International Journal of Obesity",
    issn = "0307-0565",
    publisher = "Nature Publishing Group",
    number = "2",

    }

    Dalgaard, LT, Andersen, G, Justesen, JM, Anthonsen, S, Nielsen, T, Thørner, LW, Witte, D, Jørgensen, T, Clausen, J, Lauritzen, T, Holmkvist, J, Hansen, T & Pedersen, O 2013, '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', International Journal of Obesity, bind 37, nr. 2, s. 1775-181. https://doi.org/10.1038/ijo.2012.22

    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. / Dalgaard, Louise Torp; Andersen, Gitte ; Justesen, Johanne Marie ; Anthonsen, Stine; Nielsen, Trine; Thørner, Lise Wegner; Witte, Daniel; Jørgensen, Torben; Clausen, Jesper ; Lauritzen, Torsten ; Holmkvist, Johan; Hansen, Torben; Pedersen, Oluf.

    I: International Journal of Obesity, Bind 37, Nr. 2, 21.02.2013, s. 1775-181.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity

    T2 - A study of obesity and related metabolic traits among 17,636 Danes

    AU - Dalgaard, Louise Torp

    AU - Andersen, Gitte

    AU - Justesen, Johanne Marie

    AU - Anthonsen, Stine

    AU - Nielsen, Trine

    AU - Thørner, Lise Wegner

    AU - Witte, Daniel

    AU - Jørgensen, Torben

    AU - Clausen, Jesper

    AU - Lauritzen, Torsten

    AU - Holmkvist, Johan

    AU - Hansen, Torben

    AU - Pedersen, Oluf

    PY - 2013/2/21

    Y1 - 2013/2/21

    N2 - Context: Uncoupling protein 2 (UCP2) is involved in regulating ATP-synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in β-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 analyzed within separate study populations. Results: We found no consistent associations between the UCP2 -866 G-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 OR(95% 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 -866 G-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 (IVGTT) in young Caucasian subjects (n=377) was decreased in carriers of the GG-genotype (P=0.05). Conclusions: The UCP2 -866 G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.

    AB - Context: Uncoupling protein 2 (UCP2) is involved in regulating ATP-synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in β-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 analyzed within separate study populations. Results: We found no consistent associations between the UCP2 -866 G-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 OR(95% 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 -866 G-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 (IVGTT) in young Caucasian subjects (n=377) was decreased in carriers of the GG-genotype (P=0.05). Conclusions: The UCP2 -866 G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.

    KW - UCP2

    KW - Obesity

    KW - genetics

    KW - insulin resistance

    U2 - 10.1038/ijo.2012.22

    DO - 10.1038/ijo.2012.22

    M3 - Journal article

    VL - 37

    SP - 1775

    EP - 1181

    JO - International Journal of Obesity

    JF - International Journal of Obesity

    SN - 0307-0565

    IS - 2

    ER -