Association of Common Variants of UCP2 Gene With Low-Grade Inflammation in Swedish Children and Adolescents; The European Youth Heart Study

Labayen, Idoia; Ortega, Francisco B.; Sjöstróm, Michael; Nilsson, Torbjörn; Olsson, Lovisa; Ruiz, Jonatan R.

doi:10.1203/pdr.0b013e3181b1bd35

Cited by 12 publications

(11 citation statements)

References 40 publications

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“…UCP2-knockout mice fed an atherogenic diet show significantly greater aortic atheroma formation relative to control mice, suggesting that the well-known link between dietary fuel sources and atherosclerosis is critically dependent on mitochondrial homeostasis and membrane potential. This mechanistic study was recently corroborated by a genetic epidemiologic study in humans, demonstrating that a loss of function polymorphism in UCP2 is associated with elevations in cardiovascular risk in a selected population (79).…”

Section: Atherosclerosis and Mitochondrial Rosmentioning

confidence: 64%

Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species

Widlansky

Gutterman

2011

Antioxidants & Redox Signaling

169

152

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Mitochondria are well known for their central roles in ATP production, calcium homeostasis, and heme and steroid biosynthesis. However, mitochondrial reactive oxygen species (ROS), including superoxide and hydrogen peroxide, once thought to be toxic byproducts of mitochondrial physiologic activities, have recently been recognized as important cell-signaling molecules in the vascular endothelium, where their production, conversion, and destruction are highly regulated. Mitochondrial reactive oxygen species appear to regulate important vascular homeostatic functions under basal conditions in a variety of vascular beds, where, in particular, they contribute to endothelium-dependent vasodilation. On exposure to cardiovascular risk factors, endothelial mitochondria produce excessive ROS in concert with other cellular ROS sources. Mitochondrial ROS, in this setting, act as important signaling molecules activating prothrombotic and proinflammatory pathways in the vascular endothelium, a process that initially manifests itself as endothelial dysfunction and, if persistent, may lead to the development of atherosclerotic plaques. This review concentrates on emerging appreciation of the importance of mitochondrial ROS as cell-signaling molecules in the vascular endothelium under both physiologic and pathophysiologic conditions. Future potential avenues of research in this field also are discussed. Antioxid. Redox Signal. 15, 1517-1530.

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Section: Atherosclerosis and Mitochondrial Rosmentioning

confidence: 64%

Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species

Widlansky

Gutterman

2011

Antioxidants & Redox Signaling

169

152

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“…Also, low-grade inflammation has been investigated in the context of the −866G>A polymorphism, where increased C-reactive protein (CRP) was associated with the GG-genotype in a study of 283 diabetic patients. In another study of 280 children and adolescents CRP was unaltered, but fibrinogen, complement C3 and C4 were lower in AA-carriers [106]. Finally, Rudofsky et al (2006, 2007) showed increased prevalence of the G-allele in type 1 diabetic patients, whereas there was no association with microvascular complications [105, 108].…”

Section: A Possible Role Of −866g>a Variant and Oxidative Stress Imentioning

confidence: 99%

Genetic Variance inUncoupling Protein 2in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional −866G>A Promoter Variant (rs659366)

Dalgaard

2011

Journal of Obesity

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Uncoupling proteins (UCPs) are mitochondrial proteins able to dissipate the proton gradient of the inner mitochondrial membrane when activated. This decreases ATP-generation through oxidation of fuels and may theoretically decrease energy expenditure leading to obesity. Evidence from Ucp(−/−) mice revealed a role of UCP2 in the pancreatic β-cell, because β-cells without UCP2 had increased glucose-stimulated insulin secretion. Thus, from being a candidate gene for obesity UCP2 became a valid candidate gene for type 2 diabetes mellitus. This prompted a series of studies of the human UCP2 and UCP3 genes with respect to obesity and diabetes. Of special interest was a promoter variant of UCP2 situated 866bp upstream of transcription initiation (−866G>A, rs659366). This variant changes promoter activity and has been associated with obesity and/or type 2 diabetes in several, although not all, studies. The aim of the current paper is to summarize current evidence of association of UCP2 genetic variation with obesity and type 2 diabetes, with focus on the −866G>A polymorphism.

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“…Whereas genetic and early programming features have been associated with low-grade inflammation in youth, 35,36 an active lifestyle and a desirable CRF may attenuate its effects. This has important implications for public health, as specific strategies should be developed for adolescents due to the well-known decline in PA levels during this crucial life period.…”

Section: Modelmentioning

confidence: 99%

Associations of physical activity, cardiorespiratory fitness and fatness with low-grade inflammation in adolescents: the AFINOS Study

et al. 2010

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Objective: To examine the independent associations of objectively measured physical activity (PA), cardiorespiratory fitness (CRF) and fatness with low-grade inflammatory markers in adolescents. Design: Cross-sectional study in Spain. Subjects: A sample of 192 adolescents aged 13-17 years. Measurements: PA was assessed with an accelerometer for 7 days. A 20-m shuttle-run test was used to assess CRF. Skinfold thicknesses at six sites and WCs were measured. BMI was calculated from measured height and weight. C-reactive protein (CRP), interleukin-6 (IL-6) and complement factors C3 and C4 were assayed. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Regression analysis adjusted for potential confounders and HOMA-IR was used to determine the associations between PA, CRF and fatness with low-grade inflammatory markers. Results: Total PA, vigorous PA and MVPA were positively associated with CRF (r ¼ 0.25-0.48), whereas vigorous PA was negatively associated with skinfolds (r ¼ À0.27). CRF was inversely associated with fatness, (r ¼ À0.30 to À0.48). CRF and fatness were inversely and positively associated with HOMA-IR (r ¼ À0.16 and 0.21, respectively). PA variables were not independently associated with inflammatory markers. CRF and fatness were inversely and positively associated with CRP, C3 and C4, respectively. Only body fat explained a relevant amount of the variance of the model in CRP (4%) and C4 (19%), whereas CRP and body fat jointly explained the variance in C3 (25%). All these observations were independent of HOMA-IR. Conclusions: These findings support the key role of CRF and fatness on low-grade inflammation, as well as the possible indirect role of habitual PA through CRF and body fat in adolescents.

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Association of Common Variants of UCP2 Gene With Low-Grade Inflammation in Swedish Children and Adolescents; The European Youth Heart Study

Cited by 12 publications

References 40 publications

Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species

Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species

Genetic Variance inUncoupling Protein 2in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional −866G>A Promoter Variant (rs659366)

Associations of physical activity, cardiorespiratory fitness and fatness with low-grade inflammation in adolescents: the AFINOS Study

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