MOLECULAR SCREENING IN JAPANESE AND ASIAN INDIAN NIDDM PATIENTS ASSOCIATED WITH OBESITY

The mouse obese (ob) gene has recently been isolated through the posit ional cloning technique and has been proved to result in the obese and NIDDM phenotype in mice when mutated (Nature 372:425-432, 1994). More recently, it has been demonstrated, by experiments with recombinant o b protein, that ob gene product can cause mice, including ob/ob mice, diet-induced obesity mice, and normal mice, to lower their food intake and body weight (Science 269:540-549, 1995). To investigate the genet ic and/or environmental fluences underlying the development of NIDDM a ssociated with obesity, we isolated and partially sequenced the human obese (OB) gene. The human OB gene isolated in this study encoded 167 amino acids and its open reading frame was revealed to be divided into two parts with an intermediate intron of similar to 2.4 kb. Using the single-strand conformation polymorphism (SSCP) technique, we screened Japanese and Asian Indian subjects for mutations in the protein codin g regions of the OB gene. A total of 75 NIDDM patients with obesity (5 4 Japanese and 21 Asian Indians), 40 NIDDM patients without obesity (3 4 Japanese and 6 Asian Indians), and 34 Japanese patients with simple obesity showed no abnormal SSCP patterns in either component of the co ding sequences. These results suggested that mutations in the coding r egions of the OB gene are not Likely to be commonly identifiable and t hat there would likely be a kind of obesity-associated NIDDM not cause d by mutations of the OB gene.