The Pro115Gln polymorphism within the PPAR γ2 gene has no epidemiological impact on morbid obesity

Hamer, Okka W.; Forstner, Désirée; Ottinger, Iris; Ristow, Michael; Bollheimer, Leo Cornelius; Schölmerich, Jürgen; Palitzsch, Klaus‐Dieter

doi:10.1055/s-2002-33072

Cited by 19 publications

(10 citation statements)

References 25 publications

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“…All four patients were severely obese, lending additional support to the notion that increased PPARg activity promotes increase in fat mass. It is noteworthy that in a nation-wide German epidemiological field survey, no individual homozygote or heterozygote for the 115Q allele was found, showing that this mutation is unlikely to have a significant epidemiological impact on morbid obesity [202]. However, it certainly contributes to a better understanding of the role of PPARg activity on fat mass in humans.…”

Section: Pparg Gain Of Function Mutationsmentioning

confidence: 99%

Fat poetry: a kingdom for PPARγ

2007

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Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor g (PPARg), which is a fatty acid-and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARg agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARg in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARg modulators.

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Section: Pparg Gain Of Function Mutationsmentioning

confidence: 99%

Fat poetry: a kingdom for PPARγ

2007

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“…Blüher and Paschke [Bluher and Paschke, 2003] reported an individual with the P115Q mutation who exhibited high fasting insulin levels and profound insulin resistance. However, a German cohort of 85 [Hamer et al, 2002] and 67 [Evans et al, 2000] did not find an association of P115Q with obesity. Similarly, in a French cohort of 626, P115Q was not associated with obesity [Clement et al, 2000].…”

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

Post-Translational Modifications of Nuclear Receptors and Human Disease

et al. 2012

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Nuclear receptors (NR) impact a myriad of physiological processes including homeostasis, reproduction, development, and metabolism. NRs are regulated by post-translational modifications (PTM) that markedly impact receptor function. Recent studies have identified NR PTMs that are involved in the onset and progression of human diseases, including cancer. The majority of evidence linking NR PTMs with disease has been demonstrated for phosphorylation, acetylation and sumoylation of androgen receptor (AR), estrogen receptor α (ERα), glucocorticoid receptor (GR) and peroxisome proliferator activated receptor γ (PPARγ). Phosphorylation of AR has been associated with hormone refractory prostate cancer and decreased disease-specific survival. AR acetylation and sumoylation increased growth of prostate cancer tumor models. AR phosphorylation reduced the toxicity of the expanded polyglutamine AR in Kennedy’s Disease as a consequence of reduced ligand binding. A comprehensive evaluation of ERα phosphorylation in breast cancer revealed several sites associated with better clinical outcome to tamoxifen therapy, whereas other phosphorylation sites were associated with poorer clinical outcome. ERα acetylation and sumoylation may also have predictive value for breast cancer. GR phosphorylation and acetylation impact GR responsiveness to glucocorticoids that are used as anti-inflammatory drugs. PPARγ phosphorylation can regulate the balance between growth and differentiation in adipose tissue that is linked to obesity and insulin resistance. Sumoylation of PPARγ is linked to repression of inflammatory genes important in patients with inflammatory diseases. NR PTMs provide an additional measure of NR function that can be used as both biomarkers of disease progression, and predictive markers for patient response to NR-directed treatments.

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“…Ristow et al [42] analyzed the gene for PPARG2 in 121 obese and 237 non-obese German subjects and found a Pro115Gln mutation in 4 obese and none of the control subjects. Although this finding raised the hope of having detected a major factor in the genetics of obesity, subsequently this mutation could not be found in other populations or in a larger group of the German population [43,44] . This puts doubt on the original observations.…”

Section: Missing Genetic Variation For Obesity and Related Parametersmentioning

confidence: 97%

Future Nutrigenetics: In Search of the Missing Genetic Variation

Mariman

2009

Lifestyle Genomics

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Despite considerable effort, genetic analysis of complex disorders and traits, including those related to nutrition, has revealed only a very small part of the expected genetic variation. Missing variation may occur as conditional variation depending on the presence of defined lifestyle factors, as epigenetic variation or as low-moderate effect size variation not detected by mutation screening and genome-wide association studies. Experience with genetic analysis of patients with neural tube defects provides evidence of the existence of the latter type of variation and demonstrates that candidate gene analysis is an efficient approach to discover part of this missing variation. By reviewing the genes with rare and common variation associated with obesity or related parameters, guidelines are proposed for the proper selection of candidate genes. This selection fits into an analytic strategy to deal with the complex and massive data sets expected to arise from the application of routine whole genome sequencing.

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The Pro115Gln polymorphism within the PPAR γ2 gene has no epidemiological impact on morbid obesity

Cited by 19 publications

References 25 publications

Fat poetry: a kingdom for PPARγ

Fat poetry: a kingdom for PPARγ

Post-Translational Modifications of Nuclear Receptors and Human Disease

Future Nutrigenetics: In Search of the Missing Genetic Variation

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