The agouti-related protein and body fatness in humans

被引:29
作者
Argyropoulos, G
Rankinen, T
Bai, F
Rice, T
Province, MA
Leon, AS
Skinner, JS
Wilmore, JH
Rao, DC
Bouchard, C
机构
[1] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA
[2] Washington Univ, Sch Med, Dept Genet, Div Biostat, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Psychiat, Div Biostat, St Louis, MO 63110 USA
[4] Univ Minnesota, Sch Kinesiol & Leisure Studies, Minneapolis, MN USA
[5] Indiana Univ, Dept Kinesiol, Bloomington, IN 47405 USA
[6] Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX USA
关键词
AgRP; E12/E47; promoter; polymorphism;
D O I
10.1038/sj.ijo.802201
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE: The objective of this study was to examine the impact of a single nucleotide polymorphism (SNP) (-38C>T) in the promoter of the human agouti-related protein (hAgRP) gene on promoter affinity for transcription factors (TFs) and its possible association with body composition phenotypes. DESIGN: Electrophoretic mobility shift assays for the functional studies and association analyses for the population studies. SUBJECTS AND METHODS: Nuclear extracts were isolated from the mouse hypothalamus cell line GT1-7 and subjected to binding assays using oligonucleotide probes corresponding to the -38C>T region and an antibody for the E12/E47 TFs. Individuals (n=259) from the HERITAGE Family Study were genotyped for the -38C>T SNP and used in the association studies. RESULTS: Electrophoretic mobility shift and supershift assays confirmed binding of the E12/E47 TF to the -38C>T site in a genotype-dependent manner. The T allele was found exclusively in the black subjects while the genotype with the higher binding affinity, CC, was significantly associated with high BMI, fat mass, and percent body fat in the black subjects of the HERITAGE Family Study. CONCLUSIONS: The E12/E47 TF could play a role in the regulation of hAgRP expression while the population studies suggest that the TT genotype of the -38C>T SNP could play a protective role against the development of obesity in the black population of the HERITAGE Family Study.
引用
收藏
页码:276 / 280
页数:5
相关论文
共 34 条
[1]  
ALLISON DB, 1994, INT J OBESITY, V18, P363
[2]   Differential associations of body mass index and adiposity with all-cause mortality among men in the first and second National Health and Nutrition Examination Surveys (NHANES I and NHANES II) follow-up studies [J].
Allison, DB ;
Zhu, SK ;
Plankey, M ;
Faith, MS ;
Heo, M .
INTERNATIONAL JOURNAL OF OBESITY, 2002, 26 (03) :410-416
[3]  
BOUCHARD C, 1995, MED SCI SPORT EXER, V27, P721
[4]   The gene structure and minimal promoter of the human agouti related protein [J].
Brown, AM ;
Mayfield, DK ;
Volaufova, J ;
Argyropoulos, G .
GENE, 2001, 277 (1-2) :231-238
[5]   Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat [J].
Butler, AA ;
Marks, DL ;
Fan, W ;
Kuhn, CM ;
Bartolome, M ;
Cone, RD .
NATURE NEUROSCIENCE, 2001, 4 (06) :605-611
[6]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[7]   Evidence for independent genetic influences on fat mass and body mass index in a pediatric twin sample [J].
Faith, MS ;
Pietrobelli, A ;
Nuñez, C ;
Heo, MS ;
Heymsfield, SB ;
Allison, DB .
PEDIATRICS, 1999, 104 (01) :61-67
[8]   2 RELATED HELIX-LOOP-HELIX PROTEINS PARTICIPATE IN SEPARATE CELL-SPECIFIC COMPLEXES THAT BIND THE INSULIN ENHANCER [J].
GERMAN, MS ;
BLANAR, MA ;
NELSON, C ;
MOSS, LG ;
RUTTER, WJ .
MOLECULAR ENDOCRINOLOGY, 1991, 5 (02) :292-299
[9]   Overexpression of Agrt leads to obesity in transgenic mice [J].
Graham, M ;
Shutter, JR ;
Sarmiento, U ;
Sarosi, I ;
Stark, KL .
NATURE GENETICS, 1997, 17 (03) :273-274
[10]   Long-term orexigenic effects of AgRP-(83-132) involve mechanisms other than melanocortin receptor blockade [J].
Hagan, MM ;
Rushing, PA ;
Pritchard, LM ;
Schwartz, MW ;
Strack, AM ;
Van der Ploeg, LHT ;
Woods, SC ;
Seeley, RJ .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2000, 279 (01) :R47-R52