Heterogeneous effect of peroxisome proliferator-activated receptor γ2 Ala12 variant on Type 2 diabetes risk

Ornella Ludovico, Fabio Pellegrini, Rosa Di Paola, Antonio Minenna, Sandra Mastroianno, Marina Cardellini, Maria Adelaide Marini, Francesco Andreozzi, Olga Vaccaro, Giorgio Sesti, Vincenzo Trischitta

Research output: Contribution to journalArticlepeer-review


Conflicting results have been reported regarding whether the PPARγ2 Pro12Ala polymorphism plays a role in the risk of type 2 diabetes (T2D), suggesting genetic heterogeneity. To investigate this issue, a meta-analysis of 41 published and 2 unpublished studies (a total of 42,910 subjects) was conducted. Ala12 carriers had a 19% T2D risk reduction, but this association was highly heterogeneous (p = 0.005). A great proportion (48%) of heterogeneity was explained by the controls' BMI, with risk reduction being greater when BMI was lower. Risk reduction of Ala12 carriers in Asia (35%) was higher than in Europe (15%, p = 0.02) and tended to be higher than in North America (18%, p = 0.10). Difference between Asians and Europeans was no longer significant (p = 0.15) after adjusting for the controls' BMI. Studies from Europe were still heterogeneous (p = 0.02) with risk reduction in Ala12 carriers being progressively smaller (test for trend in the odds ratios, p = 0.02) from Northern (26% reduction,p <0.0001) to Central (10%, p = 0.04) and Southern (0%, p = 0.94) Europe. In conclusion, in our meta-analysis, the reduced risk of T2D in Ala12 carriers is not homogeneous. It is greater in Asia than in Europe and, among Europeans, it is higher in Northern Europe, barely significant in Central Europe, and nonexistent in Southern Europe.

Original languageEnglish
Pages (from-to)1076-1081
Number of pages6
Issue number5
Publication statusPublished - May 2007


  • Candidate genes
  • Genetic susceptibility
  • Peroxisome proliferator-activated receptor
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics


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