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Genomic structure and mutations in adipose-specific gene, adiponectin

International Journal of Obesity volume 24, pages 861–868 (2000)Cite this article

Abstract

BACKGROUND: Adiponectin is a collagen-like plasma protein specifically synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in obesity whereas it is adipose-specific.

OBJECTIVE: To clarify the significance of the genetic variations in adiponectin gene on its plasma concentrations and obesity.

SUBJECTS: Two hundred and nineteen unrelated adult Japanese subjects (123 men and 96 women, age: 20–83 y, BMI: 16–43 kg/m2) including 77 obese subjects (BMI>26.4 kg/m2).

MEASUREMENT: Human adiponectin gene was isolated from PAC DNA pools. Mutations in the adiponectin gene were screened by direct sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin were determined by the enzyme-linked immunosorbent assay (ELISA).

RESULTS: Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and two introns. Within 2.1 kb of the 5′-flanking region, there were two octamer elements present in the promoter of adipsin. Two nucleotide changes were identified. One was a polymorphism (G/T) occurring in exon 2, and the other was a missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the subjects carrying G allele were low (G/G: 4.5 μg/ml; G/T: 5.9 μg/ml; and T/T: 6.3 μg/ml), but were not statistically significant. The allelic frequency between the obese and the non-obese showed no significant difference. The subject carrying R112C mutation showed markedly low concentration of plasma adiponectin.

CONCLUSION: Two nucleotide changes have been identified in the adiponectin gene. G/T polymorphism in exon 2 was associated with neither plasma adiponectin concentrations nor the presence of obesity. A subject carrying missense mutation (R112C) showed markedly low plasma adiponectin concentration.

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Acknowledgements

This work was supported in part by a ‘Research for the Future’ Program from The Japan Society for the Promotion of Science: JSPS-RFTF97L00801 and Grants-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan (09307019, 10557100, 10557101, 10671035).

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Authors and Affiliations

  1. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    M Takahashi, Y Arita, K Yamagata, Y Matsukawa, I Shimomura, K Hotta, H Kuriyama, S Kihara, T Nakamura, S Yamashita, T Funahashi & Y Matsuzawa

  2. Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, 463-10 Kagasuno Kawauchi-cho, Tokushima, 771-0192, Japan

    K Okutomi & M Horie

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  1. M Takahashi
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Correspondence to T Funahashi.

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Takahashi, M., Arita, Y., Yamagata, K. et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes 24, 861–868 (2000). https://doi.org/10.1038/sj.ijo.0801244

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