Obesity is a common phenomenon in Europe and North America. The increasing prevalence of obesity is, however, not confined merely to these areas. The most striking increase is seen in the pacific region. With the increment of the prevalence of obesity, type 2 diabetes is also increasing across the world. Although the prevalence of diabetes in the Papua New Guinea (PNG) population was reported to be virtually 0% (1), recent surveys showed that type 2 diabetes has become a common disease in some urban Melanesians of PNG (2,3). To clarify the genetic background of this increase of type 2 diabetes in PNG, Pro12Ala substitution in peroxisome proliferator-activated receptor (PPAR)γ2 and Trp64Arg substitution in β3-adrenergic receptor (AR) were analyzed by the PCR/restriction fragment-length polymorphism method (4,5).

Blood samples were collected from Austronesian-speaking Balopa Islanders of PNG. This study was conducted in 12 Balopa villages in 1994 with approval of the PNG Medical Advisory (6). To elucidate whether these polymorphisms were associated with obesity, the subjects were enrolled into three groups: nonobese group (20 ≤ BMI < 23 kg/m2), overweight group (25 ≤ BMI < 30), and obese group (30 ≤ BMI). The subjects who had obvious family history of obesity were omitted from the nonobese group.

The Pro12Ala substitution in PPARγ2 gene was analyzed in a total of 252 subjects (135 in the nonobese, 44 in the overweight, and 73 in the obese). Analysis of PPARγ2 had revealed that the Pro12Ala substitution was not found in any groups. We then examined Trp64Arg polymorphism in β3-AR gene. The Trp64Arg polymorphism was analyzed in a total of 175 subjects (106 in the nonobese, 21 in the overweight, and 48 in the obese). The frequencies of Trp/Trp, Trp/Arg, and Arg/Arg were 82.1%, 17.0%, and 0.9% in the nonobese group, 61.9%, 33.3%, and 4.8% in the overweight group, and 64.6%, 33.3%, and 2.1% in the obese group, respectively. The allele frequencies of the Arg64 in the nonobese, the overweight, and the obese groups were 9.4%, 21.4%, and 18.8%, respectively. The genotype frequencies of Trp/Arg and the mutant allele frequencies were significantly higher in the overweight and the obese subjects than in the nonobese subjects. There was no significant difference between the overweight subjects and the obese subjects.

Since it has been reported that the Pro12Ala substitution in PPARγ2 is associated with lower BMI, improved insulin sensitivity, and lower prevalence of type 2 diabetes (7), the Pro12Ala polymorphism in PPARγ2 is considered to have a preventive effect against the development of obesity and type 2 diabetes. The absence of the Pro12Ala substitution in PNG people had suggested that people in PNG have susceptibility to obesity and type 2 diabetes. In addition, the frequency of Trp64Arg polymorphism in the β3-AR in PNG subjects was significantly higher in the overweight and obese subjects than in the nonobese subjects. Thus, the Trp64Arg polymorphism in the β3-AR seems to be one of major genetic factors related to obesity in subjects of PNG.

As genes we had analyzed in the present study are considered to be thrifty genes, people in PNG are thought to have thrifty genotype. Austronesian-speaking people in PNG have been reported to share the same genotype with Polynesians. Therefore, it is expected that the prevalence of obesity and type 2 diabetes will increase at least to the same extent as currently seen in Polynesians with westernization of their lifestyle (8).

This work is partly supported by a grant-in-aid for Scientific Research (B) from the Japan Society for the Promotion of Science (no. 12576021).

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Address correspondence to Dr. Motoyoshi Sakaue, Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Faculty of Medical Science, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail: [email protected].

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