The Pro12Ala Polymorphism in PPAR γ2 May Confer Resistance to Type 2 Diabetes

Hara, Kazuo; Okada, Tsuneo; Tobe, Kazuyuki; Yasuda, Kazuki; Mori, Yusaku; Kadowaki, Hiroko; Hagura, Ryoko; Akanuma, Yasuo; Kimura, Satoshi; Ito, Chikako; Kadowaki, Takashi

doi:10.1006/bbrc.2000.2605

Cited by 269 publications

(228 citation statements)

References 16 publications

Supporting

Mentioning

204

Contrasting

Unclassified

Order By: Relevance

“…This Pro 12 Ala SNP has been associated with reduced transcriptional activity in vitro [17]. Discordant results have been reported in the literature [17][18][19][20][21][22][23]; however, a recent meta-analyses of 16 studies, which included over 3,000 individuals, demonstrated that the Ala allele confers protection from diabetes (21% risk reduction) [24,25]. It is possible that the environment, particularly diet or exercise habits, could modify the genotype effect and may account for a portion of the disparity found between separate studies.…”

Section: Introductionsupporting

confidence: 82%

Influence of Pro12Ala peroxisome proliferator-activated receptor γ2 polymorphism on glucose response to exercise training in type 2 diabetes

et al. 2005

View full text Add to dashboard Cite

show abstract

Section: Introductionsupporting

confidence: 82%

Influence of Pro12Ala peroxisome proliferator-activated receptor γ2 polymorphism on glucose response to exercise training in type 2 diabetes

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Angiopoietin-like proteins (ANGPTLs) are also involved in the regulation of energy homeostasis [69]. One of them, the fasting-induced adipose factor (FIAF), also called ANGPTL4, HFARP and PGAR [70][71][72][73], is most highly expressed in the adipose tissue and secreted into the circulation, where it is found associated with plasma lipoproteins. Adenovirus-mediated overexpression of FIAF was found to improve hyperinsulinemia, hyperglycemia and glucose tolerance [74].…”

Section: Adipokines Directly Involved In Energy Homeostasismentioning

confidence: 99%

“…It is noteworthy that the proband, when treated with pharmacological doses of www.cell-research.com | Cell Research Silvia I Anghel and Walter Wahli 501 npg rosiglitazone, in combination with metformin, had a good glycemic control [193]. Another well-studied variant is the PPARg 2 P12A [70,73,194,195]. This is the only well-described change found so far in the N-terminal domain of PPARg 2 .…”

Section: Pparg Loss Of Function Mutationsmentioning

confidence: 99%

“…This is the only well-described change found so far in the N-terminal domain of PPARg 2 . The initial study of Finnish and second-generation Japanese populations concluded that the less common 12A allele promotes insulin sensitivity and confers protection against type 2 diabetes [70,73,194,195]. In vitro studies showed that this allele reduces PPARg DNA binding affinity and transcriptional activity [70,73,194,195].…”

Section: Pparg Loss Of Function Mutationsmentioning

confidence: 99%

See 1 more Smart Citation

Fat poetry: a kingdom for PPARγ

2007

View full text Add to dashboard Cite

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.

show abstract

“…Therefore, the PPAR-γ gene has been viewed as a "thrifty gene", with an important role in the development of type 2 diabetes and diabetes-related traits [7,15]. Additionally, the Pro12Ala substitution in exon B of the PPAR-γ2 gene, first reported in Caucasians [16], has been associated with diabetes mellitus [17,18,19,20,21,22,23,24,25,26,27,28]. Although not all associations have been consistent, a meta-analysis of published studies has confirmed a modest (1.25-fold), but statistically significant, increase in diabetes risk for the Pro12Pro genotype [4,19].…”

Section: Introductionmentioning

confidence: 99%

Common polymorphisms of the PPAR-?2 (Pro12Ala) and PGC-1? (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial

et al. 2004

View full text Add to dashboard Cite

Aim/hypothesis. We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor γ2 (PPAR-γ2; Pro12Ala) and in PPAR-γ coactivator 1α (PGC-1α; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes. Methods. Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1α gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-γ2 gene was determined by the polymerase chain reaction-singlestrand conformation polymorphism analysis. Results. The Pro12Pro genotype of the PPAR-γ2 gene predicted the conversion to diabetes in women in the acarbose group (odds ratio 2.89, 95% CI 1.20 to 6.96; p=0.018). The 482Ser allele of the PGC-1α gene had a significant interaction with the mode of treatment (p=0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype (95% CI 1.06 to 2.33; p=0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-γ2 gene, but only the carriers of the 482Ser allele of the PGC-1α gene were responsive to acarbose treatment. Conclusion/interpretation. We conclude that the Pro12Pro genotype of the PPAR-γ2 gene and the 482Ser allele of the PGC-1α gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.

show abstract

The Pro12Ala Polymorphism in PPAR γ2 May Confer Resistance to Type 2 Diabetes

Cited by 269 publications

References 16 publications

Influence of Pro12Ala peroxisome proliferator-activated receptor γ2 polymorphism on glucose response to exercise training in type 2 diabetes

Influence of Pro12Ala peroxisome proliferator-activated receptor γ2 polymorphism on glucose response to exercise training in type 2 diabetes

Fat poetry: a kingdom for PPARγ

Common polymorphisms of the PPAR-?2 (Pro12Ala) and PGC-1? (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial

Contact Info

Product

Resources

About