Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI
Tóm tắt
The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of
We determined the complete sequence of the
The CT heterozygotes of rs11575892 had significantly higher mean BMI value (p = 0.027). After adjustment for age, gender and other significant non-genetic factors (presence of diseases), the BMI levels remained significantly higher in carriers of the rs11575892 T allele (p = 0.001). The adjusted mean BMI value of CC genotype was 27.92 ± 1.01 kg/m2 (mean, SE) as compared to 30.97 ± 1.03 kg/m2 for the CT genotype. No association was found between rs5030980 and BMI.
This study presents an association of rare allele of
Từ khóa
Tài liệu tham khảo
Hillebrand JJ, Kas MJ, Adan RA: To eat or not to eat; regulation by the melanocortin system. Physiol Behav. 2006, 89 (1): 97-102. 10.1016/j.physbeh.2006.01.034.
Seeley RJ, Drazen DL, Clegg DJ: The critical role of the melanocortin system in the control of energy balance. Annu Rev Nutr. 2004, 24: 133-149. 10.1146/annurev.nutr.24.012003.132428.
Klovins J, Haitina T, Fridmanis D, Kilianova Z, Kapa I, Fredriksson R, Gallo-Payet N, Schioth HB: The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire and synteny, as well as pharmacology and anatomical distribution of the MCRs. Mol Biol Evol. 2004, 21 (3): 563-579. 10.1093/molbev/msh050.
Stutz AM, Morrison CD, Argyropoulos G: The Agouti-related protein and its role in energy homeostasis. Peptides. 2005, 26 (10): 1771-1781. 10.1016/j.peptides.2004.12.024.
Rossi M, Kim MS, Morgan DG, Small CJ, Edwards CM, Sunter D, Abusnana S, Goldstone AP, Russell SH, Stanley SA, et al: A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Endocrinology. 1998, 139 (10): 4428-4431. 10.1210/en.139.10.4428.
Lu XY, Nicholson JR, Akil H, Watson SJ: Time course of short-term and long-term orexigenic effects of Agouti-related protein (86–132). Neuroreport. 2001, 12 (6): 1281-1284. 10.1097/00001756-200105080-00045.
Graham M, Shutter JR, Sarmiento U, Sarosi I, Stark KL: Overexpression of Agrt leads to obesity in transgenic mice. Nat Genet. 1997, 17 (3): 273-274. 10.1038/ng1197-273.
Katsuki A, Sumida Y, Gabazza EC, Murashima S, Tanaka T, Furuta M, Araki-Sasaki R, Hori Y, Nakatani K, Yano Y, et al: Plasma levels of agouti-related protein are increased in obese men. J Clin Endocrinol Metab. 2001, 86 (5): 1921-1924. 10.1210/jc.86.5.1921.
Hoggard N, Johnstone AM, Faber P, Gibney ER, Elia M, Lobley G, Rayner V, Horgan G, Hunter L, Bashir S, et al: Plasma concentrations of alpha-MSH, AgRP and leptin in lean and obese men and their relationship to differing states of energy balance perturbation. Clin Endocrinol (Oxf). 2004, 61 (1): 31-39. 10.1111/j.1365-2265.2004.02056.x.
Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS: Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997, 278 (5335): 135-138. 10.1126/science.278.5335.135.
Shutter JR, Graham M, Kinsey AC, Scully S, Luthy R, Stark KL: Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev. 1997, 11 (5): 593-602. 10.1101/gad.11.5.593.
Mayfield DK, Brown AM, Page GP, Garvey WT, Shriver MD, Argyropoulos G: A role for the Agouti-Related Protein promoter in obesity and type 2 diabetes. Biochem Biophys Res Commun. 2001, 287 (2): 568-573. 10.1006/bbrc.2001.5600.
Loos RJ, Rankinen T, Rice T, Rao DC, Leon AS, Skinner JS, Bouchard C, Argyropoulos G: Two ethnic-specific polymorphisms in the human Agouti-related protein gene are associated with macronutrient intake. Am J Clin Nutr. 2005, 82 (5): 1097-1101.
Bonilla C, Panguluri RK, Taliaferro-Smith L, Argyropoulos G, Chen G, Adeyemo AA, Amoah A, Owusu S, Acheampong J, Agyenim-Boateng K, et al: Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans. Int J Obes (Lond). 2006, 30 (4): 715-721. 10.1038/sj.ijo.0803047.
Vink T, Hinney A, van Elburg AA, van Goozen SH, Sandkuijl LA, Sinke RJ, Herpertz-Dahlmann BM, Hebebrand J, Remschmidt H, van Engeland H, et al: Association between an agouti-related protein gene polymorphism and anorexia nervosa. Mol Psychiatry. 2001, 6 (3): 325-328. 10.1038/sj.mp.4000854.
Argyropoulos G, Rankinen T, Neufeld DR, Rice T, Province MA, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C: A polymorphism in the human agouti-related protein is associated with late-onset obesity. J Clin Endocrinol Metab. 2002, 87 (9): 4198-4202. 10.1210/jc.2002-011834.
Marks DL, Boucher N, Lanouette CM, Perusse L, Brookhart G, Comuzzie AG, Chagnon YC, Cone RD: Ala67Thr polymorphism in the Agouti-related peptide gene is associated with inherited leanness in humans. Am J Med Genet A. 2004, 126 (3): 267-271. 10.1002/ajmg.a.20600.
Gauderman W, Morrison J: QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. 2006, [http://hydra.usc.edu/gxe]
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, et al: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81 (3): 559-575. 10.1086/519795.
van Rossum CT, Pijl H, Adan RA, Hoebee B, Seidell JC: Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults. Int J Obes (Lond). 2006, 30 (10): 1522-1528. 10.1038/sj.ijo.0803314.
Bai F, Rankinen T, Charbonneau C, Belsham DD, Rao DC, Bouchard C, Argyropoulos G: Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium. J Med Genet. 2004, 41 (5): 350-353. 10.1136/jmg.2003.014092.
Sozen MA, de Jonge LH, Greenway F, Ravussin E, Smith SR, Argyropoulos G: A rare mutation in AgRP, +79G>A, affects promoter activity. Eur J Clin Nutr. 2007, 61 (6): 809-812. 10.1038/sj.ejcn.1602585.
de Rijke CE, Jackson PJ, Garner KM, van Rozen RJ, Douglas NR, Kas MJ, Millhauser GL, Adan RA: Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness. Biochem Pharmacol. 2005, 70 (2): 308-316. 10.1016/j.bcp.2005.04.033.
Creemers JW, Pritchard LE, Gyte A, Le Rouzic P, Meulemans S, Wardlaw SL, Zhu X, Steiner DF, Davies N, Armstrong D, et al: Agouti-related protein is posttranslationally cleaved by proprotein convertase 1 to generate agouti-related protein (AGRP)83-132: interaction between AGRP83-132 and melanocortin receptors cannot be influenced by syndecan-3. Endocrinology. 2006, 147 (4): 1621-1631. 10.1210/en.2005-1373.
Goto K, Inui A, Takimoto Y, Yuzuriha H, Asakawa A, Kawamura Y, Tsuji H, Takahara Y, Takeyama C, Katsuura G, et al: Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats. Int J Mol Med. 2003, 12 (3): 379-383.