A role for the Agouti-Related Protein promoter in obesity and type 2 diabetes

Douglas K. Mayfield; Angela M. Brown; Grier P. Page; W. Timothy Garvey; Mark D. Shriver; George Argyropoulos

doi:10.1006/bbrc.2001.5600

A role for the Agouti-Related Protein promoter in obesity and type 2 diabetes

Douglas K. Mayfield, Angela M. Brown, Grier P. Page, W. Timothy Garvey, Mark D. Shriver, George Argyropoulos

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Abstract

The murine Agouti-Related Protein (mAGRP) is upregulated in obese and diabetic mice and can stimulate hyperphagia when overexpressed in transgenic models. Here we report upstream nucleotide sequences of the human hAGRP gene with putative recognition sites for transcription factors including a site for the STAT transactivators. A polymorphism (-38C→T) was identified in the promoter region and the C/C genotype had significantly higher promoter activity and affinity for transcription factors as tested in periphery- and hypothalamus-derived cell lines. The polymorphic site could affect the expression levels of hAGRP and the high expressing C/C genotype was significantly associated with high BMI and type 2 diabetes in Africans.

Original language	English (US)
Pages (from-to)	568-573
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	287
Issue number	2
DOIs	https://doi.org/10.1006/bbrc.2001.5600
State	Published - Sep 21 2001

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1006/bbrc.2001.5600

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title = "A role for the Agouti-Related Protein promoter in obesity and type 2 diabetes",

abstract = "The murine Agouti-Related Protein (mAGRP) is upregulated in obese and diabetic mice and can stimulate hyperphagia when overexpressed in transgenic models. Here we report upstream nucleotide sequences of the human hAGRP gene with putative recognition sites for transcription factors including a site for the STAT transactivators. A polymorphism (-38C→T) was identified in the promoter region and the C/C genotype had significantly higher promoter activity and affinity for transcription factors as tested in periphery- and hypothalamus-derived cell lines. The polymorphic site could affect the expression levels of hAGRP and the high expressing C/C genotype was significantly associated with high BMI and type 2 diabetes in Africans.",

author = "Mayfield, {Douglas K.} and Brown, {Angela M.} and Page, {Grier P.} and Garvey, {W. Timothy} and Shriver, {Mark D.} and George Argyropoulos",

note = "Funding Information: Errol Y. Morrison and Mr. Bernard Owen of the Jamaican Diabetes Association and the people of Jamaica, the Gullah-speaking African Americans of South Carolina, Mr. Kirby J. Smith, and the nurses of Project Sugar in South Carolina. We would also like to thank Drs. R. Gill, E. Ravussin, C. Bouchard, D. York, S. Smith, T. Rankinen, A. Colakun, and J. Volaufova for helpful discussions. This project was supported in part by a U.S. Army grant to the Pennington Biomedical Research Center (DAMD 17-97-2-7013).",

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AU - Page, Grier P.

AU - Garvey, W. Timothy

AU - Shriver, Mark D.

AU - Argyropoulos, George

N1 - Funding Information: Errol Y. Morrison and Mr. Bernard Owen of the Jamaican Diabetes Association and the people of Jamaica, the Gullah-speaking African Americans of South Carolina, Mr. Kirby J. Smith, and the nurses of Project Sugar in South Carolina. We would also like to thank Drs. R. Gill, E. Ravussin, C. Bouchard, D. York, S. Smith, T. Rankinen, A. Colakun, and J. Volaufova for helpful discussions. This project was supported in part by a U.S. Army grant to the Pennington Biomedical Research Center (DAMD 17-97-2-7013).

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N2 - The murine Agouti-Related Protein (mAGRP) is upregulated in obese and diabetic mice and can stimulate hyperphagia when overexpressed in transgenic models. Here we report upstream nucleotide sequences of the human hAGRP gene with putative recognition sites for transcription factors including a site for the STAT transactivators. A polymorphism (-38C→T) was identified in the promoter region and the C/C genotype had significantly higher promoter activity and affinity for transcription factors as tested in periphery- and hypothalamus-derived cell lines. The polymorphic site could affect the expression levels of hAGRP and the high expressing C/C genotype was significantly associated with high BMI and type 2 diabetes in Africans.

AB - The murine Agouti-Related Protein (mAGRP) is upregulated in obese and diabetic mice and can stimulate hyperphagia when overexpressed in transgenic models. Here we report upstream nucleotide sequences of the human hAGRP gene with putative recognition sites for transcription factors including a site for the STAT transactivators. A polymorphism (-38C→T) was identified in the promoter region and the C/C genotype had significantly higher promoter activity and affinity for transcription factors as tested in periphery- and hypothalamus-derived cell lines. The polymorphic site could affect the expression levels of hAGRP and the high expressing C/C genotype was significantly associated with high BMI and type 2 diabetes in Africans.

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A role for the Agouti-Related Protein promoter in obesity and type 2 diabetes

Abstract

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