Molecular screening of both the promoter and the protein coding regions in the human ob gene in Japanese obese subjects with non-insulin-dependent diabetes mellitus

M. Shigemoto, S. Nishi, Y. Ogawa, N. Isse, N. Matsuoka, T. Tanaka, N. Azuma, H. Masuzaki, H. Nishimura, Y. Yoshimasa, K. Hosoda, K. Nakao

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Abstract

Objective: Although the molecular mechanism of obesity has been poorly understood, recent studies indicate that leptin plays a critical role in regulating both food intake and body weight. Because obesity decreases the sensitivity to insulin, the human ob gene is presumed to be one of the candidate genes for non-insulin-dependent diabetes mellitus (NIDDM) associated with obesity. Although the protein coding region in the ob gene has been screened for mutations, the promoter region and the noncoding first exon have not yet been studied. We investigated the involvement of the human ob gene, especially mutations at the promoter region and the non-coding first exon, in the development of NIDDM associated with obesity. Subjects: The study group comprised 60 Japanese obese subjects with NIDDM (body mass index (BMI) 43.6≤BMI≤26.4, 29.0±0.41 (mean±S.E.M.)) and 24 obese individuals with impaired glucose tolerance (IGT) (30≤BMI≤26.4, 27.1±0.22). Methods: Mutations at both the promoter region and all three exons in the human ob gene were screened by the single-stranded conformational polymorphism analysis. When aberrantly migrated bands were recognized, the PCR-amplified DNA fragment was directly sequenced. Results: In the protein coding region a silent mutation in the second exon was detected. The noncoding first exon and the about 100 bp 5'-flanking region of the gene which contains a proximal CCAAT/enhancer-binding protein site were screened, but no mutations were found. Conclusion: These results suggest that no mutations in either the promoter region at the about 100 bp 5'-flanking region of the gene, or in any of the three exons, are involved in the development of NIDDM or IGT associated with obesity.

Original languageEnglish
Pages (from-to)511-513
Number of pages3
JournalEuropean journal of endocrinology
Volume137
Issue number5
DOIs
Publication statusPublished - Nov 1997

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Shigemoto, M., Nishi, S., Ogawa, Y., Isse, N., Matsuoka, N., Tanaka, T., Azuma, N., Masuzaki, H., Nishimura, H., Yoshimasa, Y., Hosoda, K., & Nakao, K. (1997). Molecular screening of both the promoter and the protein coding regions in the human ob gene in Japanese obese subjects with non-insulin-dependent diabetes mellitus. European journal of endocrinology, 137(5), 511-513. https://doi.org/10.1530/eje.0.1370511