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

• DOI: 10.1006/bbrc.2000.2605
• Publication Date: 2002-09-16T14:49:19Z
• Authors: Kazuo Hara; Terumasa Okada; Kazuyuki Tobe; Kazuki Yasuda; Yasumichi Mori; Hiroko Kadowaki; Ryoko Hagura; Yasuo Akanuma; Satoshi Kimura; Chikako Ito; Takashi Kadowaki
• Keywords: Male; 2. Zero hunger; 0303 health sciences; Polymorphism, Genetic; Genotype; Receptors, Cytoplasmic and Nuclear; Immunity, Innate; 03 medical and health sciences; Diabetes Mellitus, Type 2; Japan; Case-Control Studies; Humans; Insulin; Female; Obesity; Alleles; Aged; Transcription Factors

Peroxisome proliferator-activated receptor gamma (PPARgamma) has been implicated in adipocyte differentiation. Recently it was reported that heterozygous deficiency of PPARgamma led to the protection from high-fat diet-induced insulin resistance in an animal model. A Pro12Ala polymorphism has been detected in the human PPARgamma2 gene. Since this amino acid substitution may cause a reduction in the transcriptional activity of PPARgamma, this polymorphism may be associated with decreased insulin resistance and decreased risk of type 2 diabetes. To investigate this hypothesis, we performed a case-control study of the Pro12Ala PPARgamma2 polymorphism in Japanese diabetic and non-diabetic subjects. The frequency of Ala12 was significantly lower in the diabetic group. In an overweight or obese group, subjects with Ala12 were more insulin sensitive than those without. These results suggest that the PPARgamma is a thrifty gene and that the Pro12Ala PPARgamma2 polymorphism protects against type 2 diabetes in the Japanese.