A role for the Agouti-Related Protein promoter in obesity and type 2 diabetes.
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.
Mayfield
D K
DK
Department of Medicine, Strom Thurmond Biomedical Research Center, Medical University of South Carolina, 114 Doughty Street, Charleston, South Carolina 29403, USA.
Brown
A M
AM
Page
G P
GP
Garvey
W T
WT
Shriver
M D
MD
Argyropoulos
G
G
D054369:Agouti-Related Protein; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D004247:DNA / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D011506:Proteins / Q000235:genetics* / Q000502:physiology
C515198:AGRP protein, human; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D004247:DNA