Heterogeneous effect of peroxisome proliferator-activated receptor gamma2 Ala12 variant on type 2 diabetes risk.
Conflicting results have been reported regarding whether the PPARgamma2 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 To investigate this issue, a meta-analysis of 41 published and 2 unpublished studies (a total of 42,910 subjects) was conducted.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.
Ludovico
Ornella
O
Unit of Endocrinology, Scientific Institute "Casa Sollievo della Sofferenza," Viale Cappuccini, S. Giovanni Rotondo, 71013 Italy. ornilud@libero.it
Pellegrini
Fabio
F
Di Paola
Rosa
R
Minenna
Antonio
A
Mastroianno
Sandra
S
Cardellini
Marina
M
Marini
Maria Adelaide
MA
Andreozzi
Francesco
F
Vaccaro
Olga
O
Sesti
Giorgio
G
Trischitta
Vincenzo
V
D019943:Amino Acid Substitution; D016001:Confidence Intervals; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004032:Diet; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D047495:PPAR gamma / Q000235:genetics*; D012016:Reference Values; D018570:Risk Assessment; D044465:White People
D047495:PPAR gamma