PURPOSE OF REVIEW: To provide a timely update of the literature regarding the role of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma gene in type 2 diabetes and related phenotypes. RECENT FINDINGS: The adipocyte-specific gamma2 isoform of peroxisome proliferator-activated receptor gamma is now considered to be one of the best-replicated genetic risk factors of common type 2 diabetes. The effect is relatively weak (pooled odds ratio is about 1.2) but because of the high prevalence and population-attributable risk, this polymorphism becomes relevant for assessing genetic susceptibility for type 2 diabetes. Less clear is the association with prediabetes subphenotypes where effects were only detectable in selected subgroups. Furthermore this review gives an overview about possible mechanisms of peroxisome proliferator-activated receptor gamma effects, gene-environment interactions, relevance to the therapeutic response to thiazolidinediones and further clinical observations. SUMMARY: In conclusion, the Pro12 allele of peroxisome proliferator-activated receptor gamma is a robust diabetes-risk allele, as confirmed by many replications. There are many more clinical observations related to the Pro12Ala genotype which could be interesting and these clearly need to be analyzed in future studies.
PURPOSE OF REVIEW: To provide a timely update of the literature regarding the role of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma gene in type 2 diabetes and related phenotypes. RECENT FINDINGS: The adipocyte-specific gamma2 isoform of peroxisome proliferator-activated receptor gamma is now considered to be one of the best-replicated genetic risk factors of common type 2 diabetes. The effect is relatively weak (pooled odds ratio is about 1.2) but because of the high prevalence and population-attributable risk, this polymorphism becomes relevant for assessing genetic susceptibility for type 2 diabetes. Less clear is the association with prediabetes subphenotypes where effects were only detectable in selected subgroups. Furthermore this review gives an overview about possible mechanisms of peroxisome proliferator-activated receptor gamma effects, gene-environment interactions, relevance to the therapeutic response to thiazolidinediones and further clinical observations. SUMMARY: In conclusion, the Pro12 allele of peroxisome proliferator-activated receptor gamma is a robust diabetes-risk allele, as confirmed by many replications. There are many more clinical observations related to the Pro12Ala genotype which could be interesting and these clearly need to be analyzed in future studies.
Authors: Rita S Strakovsky; Stéphane Lezmi; Ielyzaveta Shkoda; Jodi A Flaws; William G Helferich; Yuan-Xiang Pan Journal: J Nutr Biochem Date: 2015-06-20 Impact factor: 6.048
Authors: Jakub J Regieli; J Wouter Jukema; Pieter A Doevendans; Aeilko H Zwinderman; Yolanda van der Graaf; John J Kastelein; Diederick E Grobbee Journal: Diabetes Care Date: 2009-02-19 Impact factor: 19.112
Authors: Ulla Vogel; Stine Segel; Claus Dethlefsen; Anne Tjønneland; Anne Thoustrup Saber; Håkan Wallin; Majken K Jensen; Erik B Schmidt; Paal Skytt Andersen; Kim Overvad Journal: BMC Med Genet Date: 2009-06-07 Impact factor: 2.103