Pro12Ala Substitution in the Peroxisome Proliferator-Activated Receptor-Gamma Is Associated with Increased Leptin Levels in Women with Type-2 Diabetes mellitus

Simón, I; Vendrell, Joan; Gutiérrez, C.; Fernández-Real, José Manuel; Vendrell, Iolanda; Gallart, Lluís; Fontova, Ramón; Richart, C

doi:10.1159/000064490

Cited by 67 publications

(27 citation statements)

References 33 publications

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“…Indeed, it was shown, in vivo , that Ala12 allele is associated with a reduced LPL activity in postheparin plasma [93]; higher leptin levels were observed in Pro12Ala compared to Pro12Pro carrier women [92]. The effect of Pro12Ala on increased leptin levels is likely to be supported by a study in women with functional hyperandrogenism (FOH), in which the authors demonstrated that Ala allele was more frequent in FOH women than in healthy controls (36% versus 28%) and that leptin levels were higher in nonobese FOH women compared to controls [100].…”

Section: Pparg Target Genes: Polymorphisms Haplotypes and Gene Ementioning

confidence: 99%

PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

et al. 2010

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Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most extensively studied ligand-inducible transcription factors (TFs), able to modulate its transcriptional activity through conformational changes. It is of particular interest because of its pleiotropic functions: it plays a crucial role in the expression of key genes involved in adipogenesis, lipid and glucid metabolism, atherosclerosis, inflammation, and cancer. Its protein isoforms, the wide number of PPARγ target genes, ligands, and coregulators contribute to determine the complexity of its function. In addition, the presence of genetic variants is likely to affect expression levels of target genes although the impact of PPARG gene variations on the expression of target genes is not fully understood. The introduction of massively parallel sequencing platforms—in the Next Generation Sequencing (NGS) era—has revolutionized the way of investigating the genetic causes of inherited diseases. In this context, DNA-Seq for identifying—within both coding and regulatory regions of PPARG gene—novel nucleotide variations and haplotypes associated to human diseases, ChIP-Seq for defining a PPARγ binding map, and RNA-Seq for unraveling the wide and intricate gene pathways regulated by PPARG, represent incredible steps toward the understanding of PPARγ in health and disease.

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Section: Pparg Target Genes: Polymorphisms Haplotypes and Gene Ementioning

confidence: 99%

PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

et al. 2010

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“…Adipose-derived cytokines leptin and adiponectin levels have been shown to increase insulin action [184, 185]. Indeed, Ala12 allele is associated with higher plasma levels of leptin in Spanish diabetic women [186]. In comparison, two Japanese population studies show that Ala12 allele carriers have significantly lower plasma levels of adiponectin than Pro12 allele carriers [187, 188] and another two case-control studies in either diabetic patients or women with PCOS fail to find significant change in serum adiponectin levels [189, 190].…”

Section: Cellular Mechanism Of Pparγ2pro12ala Polymorphismmentioning

confidence: 99%

PPARγ2^Pro12Ala Polymorphism and Human Health

2009

PPAR Research

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The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPARγ2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPARγ2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPARγ2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.

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“…Previous studies demonstrated that the PPARG Pro12Ala variant allele is associated with higher insulin sensitivity, lower body mass index (BMI) (11), decreased risk of T2DM (12)(13)(14), higher high-density cholesterol (HDL) levels (11) and decreased incidence of CVD (15). Additionally, it was demonstrated that the PPARG Pro12Ala polymorphism may alter the plasma levels of leptin, adiponectin, resistin and ghrelin (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome

et al. 2013

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Abstract. Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

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Pro12Ala Substitution in the Peroxisome Proliferator-Activated Receptor-Gamma Is Associated with Increased Leptin Levels in Women with Type-2 Diabetes mellitus

Cited by 67 publications

References 33 publications

PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

PPARγ2^Pro12Ala Polymorphism and Human Health

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome

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Pro12Ala Substitution in the Peroxisome Proliferator-Activated Receptor-Gamma Is Associated with Increased Leptin Levels in Women with Type-2 Diabetes mellitus

Cited by 67 publications

References 33 publications

PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

PPARγ2Pro12Ala Polymorphism and Human Health

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome

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PPARγ2^Pro12Ala Polymorphism and Human Health