The Proline 12 Alanine Substitution in the Peroxisome Proliferator–Activated Receptor-γ2 Gene Is Associated With Lower Lipoprotein Lipase Activity in Vivo

Schneider, Jochen G.; Kreuzer, Joerg; Hamann, Andreas; Nawroth, Peter P.; Dugi, Klaus A.

doi:10.2337/diabetes.51.3.867

Cited by 45 publications

(25 citation statements)

References 21 publications

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“…The ES has been shown to correlate better with risk factors of CAD than other scores ( Sullivan et al, 1990 ). Biochemical parameters and the Pro12Ala genotype in exon B of PPAR γ 2 were determined as described elsewhere ( Schneider et al, 2002 ). The study was approved by the Internal Ethics Committee of Heidelberg University.…”

Section: Resultsmentioning

confidence: 99%

The Proline 12 Alanine Substitution in the PPARγ2 Gene is Associated With Increased Extent of Coronary Artery Disease in Men

Schneider

Schiekofer²,

Eynatten³

et al. 2009

Exp Clin Endocrinol Diabetes

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Section: Resultsmentioning

confidence: 99%

The Proline 12 Alanine Substitution in the PPARγ2 Gene is Associated With Increased Extent of Coronary Artery Disease in Men

Schneider

Schiekofer²,

Eynatten³

et al. 2009

Exp Clin Endocrinol Diabetes

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“…While some studies report enhanced suppression of lipolysis and hence adipose lipid trapping in Ala carriers (121,122), others have detected no difference in fasting FFAs (122) or response to oral lipid (103), while another actually found lower post-heparin plasma lipoprotein lipase activity in Ala carriers (123). Although differences in adipocytokine levels are an attractive explanation for genotypespecific metabolic responses, the reported relationship of Pro12Ala genotype to plasma adiponectin has not been consistent (124,125).…”

Section: Common Variants In Pparγ and Human Metabolic Diseasementioning

confidence: 85%

PPAR and human metabolic disease

Semple

Chatterjee²,

O’Rahilly³

2006

Journal of Clinical Investigation

765

548

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The nuclear receptor family of PPARs was named for the ability of the original member to induce hepatic peroxisome proliferation in mice in response to xenobiotic stimuli. However, studies on the action and structure of the 3 human PPAR isotypes (PPARα, PPARδ, and PPARγ) suggest that these moieties are intimately involved in nutrient sensing and the regulation of carbohydrate and lipid metabolism. PPARα and PPARδ appear primarily to stimulate oxidative lipid metabolism, while PPARγ is principally involved in the cellular assimilation of lipids via anabolic pathways. Our understanding of the functions of PPARγ in humans has been increased by the clinical use of potent agonists and by the discovery of both rare and severely deleterious dominant-negative mutations leading to a stereotyped syndrome of partial lipodystrophy and severe insulin resistance, as well as more common sequence variants with a much smaller impact on receptor function. These may nevertheless have much greater significance for the public health burden of metabolic disease. This Review will focus on the role of PPARγ in human physiology, with specific reference to clinical pharmacological studies, and analysis of PPARG gene variants in the abnormal lipid and carbohydrate metabolism of the metabolic syndrome.

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“…The Pro12Ala polymorphism in PPARG may lead to an alteration of the intrinsic activity of this receptor. Presence of the Ala allele is associated with reduced lipoprotein lipase activity, resulting in altered clearance of low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), with consequent increase in lipoprotein plasma levels [6]. These changes in lipid metabolism in subjects carrying the Ala allele were confirmed by a meta-analysis with 48,210 individuals, which included association studies between the Pro12Ala polymorphism and lipid profile published until May 2014 [7].…”

Section: Introductionmentioning

confidence: 66%

Polymorphisms in PPARG and APOE: relationships with lipid profile of adolescents with cardiovascular risk factors

Alves

Morais

Augusto

et al. 2017

Nutrire

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Background: Cardiovascular diseases constitute the main death cause worldwide resulting from a combination of genetic and lifestyle factors, and the prevalence among younger individuals has increased. It is important to early identify changes in lipid profile and the influence of genetic variations in specific genes on the individual patterns of lipid profile. Thus, the aim of this study was to verify the relationship of polymorphisms in PPAR-gamma gene (PPARG − rs1801282 − Pro12Ala) and in apolipoprotein E gene (APOE − rs429358 + rs7412, determinants of the APOE2, APOE3, or APOE4 genotypes) with lipid profile of adolescents under cardiovascular risk factors. Methods: This was a cross-sectional study with 115 adolescents aged 10-19 years, which presented cardiovascular risk factors. The students were evaluated regarding socioeconomic, anthropometric, biochemical, genetic, and dietetic variables. Student's t test or Mann-Whitney test were applied to the analysis of the genotypes. Multiple linear regression analysis was performed to determine the variables that most influenced the lipid profile. Results: Adolescents carrying PPARG Ala allele showed higher serum triglycerides (p = 0.0423) and very low-density lipoprotein (p = 0.0410) levels when compared to those carrying the wild genotype. For the APOE polymorphism, it was observed a trend of higher triglycerides (p = 0.0712) and very low-density lipoprotein (p = 0.0758) levels in the adolescents carrying the E4 allele when compared to those who did not carry this allele. Conclusion: The polymorphisms PPARG rs1801282 and APOE rs429358 + rs7412 seem to be related to the development of lipid profile alterations in adolescents.

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The Proline 12 Alanine Substitution in the Peroxisome Proliferator–Activated Receptor-γ2 Gene Is Associated With Lower Lipoprotein Lipase Activity in Vivo

Cited by 45 publications

References 21 publications

The Proline 12 Alanine Substitution in the PPARγ2 Gene is Associated With Increased Extent of Coronary Artery Disease in Men

The Proline 12 Alanine Substitution in the PPARγ2 Gene is Associated With Increased Extent of Coronary Artery Disease in Men

PPAR and human metabolic disease

Polymorphisms in PPARG and APOE: relationships with lipid profile of adolescents with cardiovascular risk factors

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