Differential effect of PPARgamma2 variants in the development of type 2 diabetes between native Japanese and Japanese Americans.

Common type 2 diabetes mellitus is a disorder that is though to develop by interaction between genetic and environmental factors. Among these factors, peroxisome proliferator-activated receptor (PPAR)gamma gene was identified as a genetic element which variant form, Pro12Ala, was shown to have differential metabolic activity than the wild type. To elucidate the mechanism of interaction between genetic and environmental factors in development of type 2 diabetes, we analyzed prevalence and metabolic status in the context of the variant form of PPARgamma in 105 native Japanese and 145 Japanese American, both should have different environmental factors. The observed frequency of Pro-allele in Japanese American with diabetes was significantly higher than those with normal glucose tolerance (NGT) (P=0.015), while that in native Japanese with diabetes was not different from those with NGT. Alternatively, Japanese Americans with diabetes with Pro/Pro genotype had significantly higher BMI (P=0.024) and higher fasting serum insulin (P=0.043) level than native Japanese, showing that individuals with Ala-allele could be more sensitive to insulin than those with Pro/Pro genotype. The data with emigrants suggests the possible interaction of gene-environment in the development of type 2 diabetes.