Subscribe to RSS
DOI: 10.1055/s-2007-992785
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Genetic Polymorphisms of β2- and β3-Adrenergic Receptor Genes Associated with Characteristics of the Metabolic Syndrome in Black South African Women
Publication History
received 27.08.2007
first decision 11.10.2007
accepted 17.10.2007
Publication Date:
07 April 2008 (online)
Abstract
Background: Genetic variation in the β2 (ADRB2) and β3 (ADRB3) adrenergic receptor genes are associated with obesity and insulin resistance. To further elucidate the role of these genes in the pathophysiology of obesity the present study investigated associations between certain polymorphisms in ADRB2 and ADRB3 and parameters of carbohydrate and lipid metabolism in a population of African origin.
Material and Methods: Data of 102 black South African women obtained in the POWIRS (Profile of Obese Women with the Insulin Resistance Syndrome) study were used. Endpoint measurements included several anthropometric variables, resting blood pressure, plasma glucose, insulin, free fatty acids (FFA), ghrelin, leptin and lipids, and insulin resistance as estimated by the homeostasis model assessment (HOMA-IR) index. Polymorphisms were analyzed via PCR based methods.
Results: The percentage body fat was significantly lower (p≤0.05) and the FFA significantly higher (p≤0.05) in lean subjects (BMI≤25 kg/m2) with the Glu27 variant allele compared to subjects with the Gln27 wildtype allele of the ADRB2 gene. In contrast, the variant allele of the ADRB2 gene was significantly positive associated (p≤0.05) with the HOMA-IR-index in overweight black African women (BMI>25 kg/m2). No significant differences in parameters of the metabolic syndrome were apparent between subjects with the wildtype and variant alleles in the ADRB3 gene.
Conclusion: The presence of the Glu27 and Arg64 polymorphisms of the ADRB2 and ADRB3 genes are not directly related to indices of the metabolic syndrome.
Key words
black African women - ADRB genotypes - adrenoceptors - polymorphism - metabolic syndrome - carbohydrate and lipid metabolism
References
- 1 Allison DB, Heo M. et al . Meta-analysis of the association of the Trp64Arg polymorphism in the beta3 adrenergic receptor with body mass index. Int J Obes Relat Metab Disord. 1998; 22 ((6)) 559-566
- 2 Arner P, Hoffstedt J. Adrenoceptor genes in human obesity. J Intern Med. 1999; 245 ((6)) 667-672
- 3 Boileau RA, Lohman TG. et al . Exercise and body composition of children and youth. Scand J Sport Sci. 1985; 7 17-27
- 4 Bornstein SR, Schuppenies A. et al . Approaching the shared biology of obesity and depression: the stress axis as the locus of gene-environment interactions. Mol Psychiatry. 2006; 11 ((10)) 892-902
- 5 Bornstein SR, Wong ML. et al . 150 years of Sigmund Freud: What would Freud have said about the obesity epidemic?. Mol Psychiatry. 2006; 11 ((12)) 1070-1072
- 6 Clement K, Vaisse C. et al . Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med. 1995; 333 ((6)) 352-354
- 7 Fisher E, Li Y. et al . Preliminary evidence of FABP2 A54 T polymorphism associated with reduced risk of type 2 diabetes and obesity in women from a German cohort. Horm Metab Res. 2006; 38 ((5)) 341-345
- 8 Galletti F, Iacone R. et al . Lack of association between polymorphism in the beta2-adrenergic receptor gene, hypertension, and obesity in the Olivetti heart study. Am J Hypertens. 2004; 17 ((8)) 718-720
- 9 Gonzalez Sanchez JL, Proenza AM. et al . The glutamine 27 glutamic acid polymorphism of the beta2-adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population-based study in Spain. Clin Endocrinol (Oxf). 2003; 59 ((4)) 476-481
- 10 Gouni-Berthold I, Giannakidou E. et al . The K121Q polymorphism of the plasma cell glycoprotein-1 gene is not associated with diabetes mellitus type 2 in German Caucasians. Horm Metab Res. 2006; 38 ((8)) 524-529
- 11 Ishiyama-Shigemoto S, Yamada K. et al . Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia. 1999; 42 ((1)) 98-101
- 12 Jost MM, Jost P. et al . The beta3-adrenergic agonist CL316,243 inhibits insulin signaling but not glucose uptake in primary human adipocytes. Exp Clin Endocrinol Diabetes. 2005; 113 ((8)) 418-422
- 13 Kasznicki J, Blasiak J. et al . The Trp64Arg beta3-adrenergic receptor amino-acid variant is not associated with overweight and type 2 diabetes mellitus in Polish population. Exp Clin Endocrinol Diabetes. 2005; 113 ((10)) 593-597
- 14 Kiessling A, Ehrhart-Bornstein M. Transcription factor 7-like 2 (TCFL2) - a novel factor involved in pathogenesis of type 2 diabetes. Comment on: Grant et al., Nature Genetics 2006, Published online 15 January 2006. Horm Metab Res. 2006; 38 ((2)) 137-138
- 15 Kim SH, Kim DJ. et al . Significance of beta2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects. Metabolism. 2002; 51 ((7)) 833-837
- 16 Korenblum W, Barthel A. et al . Elevated cortisol levels and increased rates of diabetes and mood symptoms in Soviet Union-born Jewish immigrants to Germany. Mol Psychiatry. 2005; 10 ((11)) 974-975
- 17 Kruger HS, Venter CS. et al . Obesity in African women in the North West Province, South Africa is associated with an increased risk of non-communicable diseases: the THUSA study. Transition and Health during Urbanisation of South Africans. Br J Nutr. 2001; 86 ((6)) 733-740
- 18 Lamounier-Zepter V, Ehrhart-Bornstein M. et al . Metabolic syndrome and the endocrine stress system. Horm Metab Res. 2006; 38 ((7)) 437-441
- 19 Lange LA, Norris JM. et al . Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study. Int J Obes (Lond). 2005; 29 ((5)) 449-457
- 20 Large V, Hellstrom L. et al . Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. J Clin Invest. 1997; 100 ((12)) 3005-3013
- 21 Leineweber K, Buscher R. et al . Beta-adrenoceptor polymorphisms. Naunyn Schmiedebergs Arch Pharmacol. 2004; 369 ((1)) 1-22
- 22 Li Y, Fisher E. et al . Association between functional FABP2 promoter haplotype and type 2 diabetes. Horm Metab Res. 2006; 38 ((5)) 300-307
- 23 Lima JJ, Feng H. et al . Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism. 2007; 56 ((6)) 757-765
- 24 Malczewska-Malec M, Wybranska I. et al . An analysis of the link between polymorphisms of the beta2 and beta3 adrenergic receptor gene and metabolic parameters among Polish Caucasians with familial obesity. Med Sci Monit. 2003; 9 ((6)) CR225-34
- 25 Matthews DR, Hosker JP. et al . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28 ((7)) 412-419
- 26 Meirhaeghe A, Helbecque N. et al . Impact of polymorphisms of the human beta2-adrenoceptor gene on obesity in a French population. Int J Obes Relat Metab Disord. 2000; 24 ((3)) 382-387
- 27 Munakata M, Harada Y. et al . Molecular-based haplotype analysis of the beta 2-adrenergic receptor gene (ADRB2) in Japanese asthmatic and non-asthmatic subjects. Allergol Int. 2006; 55 ((2)) 191-198
-
28 Norton K, Olds T.
Anthropometrica. A textbook of body measurement for sports and health courses . Sydney, University of New South Wales Press 1996 - 29 Olckers A, Towers GW. et al . Protective effect against type 2 diabetes mellitus identified within the ACDC gene in a black South African diabetic cohort. Metabolism. 2007; 56 ((5)) 587-592
- 30 Ongphiphadhanakul B, Rajatanavin R. et al . Relation of beta3-adrenergic receptor gene mutation to total body fat but not percent body fat and insulin levels in Thais. Metabolism. 1999; 48 ((5)) 564-567
- 31 Podolsky RH, Barbeau P. et al . Candidate genes and growth curves for adiposity in African- and European-American youth. Int J Obes (Lond). 2007; 31 ((10)) 1491-1499
- 32 Reichel A, Schwarz J. et al . Depression and anxiety symptoms in diabetic patients on continuous subcutaneous insulin infusion (CSII). Mol Psychiatry. 2005; 10 ((11)) 975-976
- 33 Rupert JL, Monsalve MV. et al . Beta2-adrenergic receptor allele frequencies in the Quechua, a high altitude native population. Ann Hum Genet. 2000; 64 ((Pt 2)) 135-143
- 34 Santos JL, Perez-Bravo F. et al . No evidence for an association between genetic polymorphisms of beta(2)- and beta(3)-adrenergic receptor genes with body mass index in Aymara natives from Chile. Nutrition. 2002; 18 ((3)) 255-258
- 35 Schutte AE, Kruger HS. et al . The emergence of the metabolic syndrome in urban obese African women: The POWIRS-study. S Afr J Sci. 2005; 101 61-67
- 36 Schwarz PE, Bornstein SR. et al . Elevated fasting glucose levels predicts IGT and diabetes also in middle-age subjects. Diabetes Res Clin Pract.. 2006;
- 37 Schwarz PE, Govindarajalu S. et al . Haplotypes in the promoter region of the ADIPOQ gene are associated with increased diabetes risk in a German Caucasian Population. Horm Metab Res. 2006; 38 ((7)) 447-451
- 38 Schwarz PE, Schwarz J. et al . Diabetes prevention-from physiology to implementation. Horm Metab Res. 2006; 38 ((7)) 460-464
- 39 Schwarz PE, Schwarz J. et al . Development of a diabetes prevention management program for clinical practice. Public Health Rep. 2007; 122 ((2)) 258-263
- 40 Schwarz PE, Towers GW. et al . Hypoadiponectinemia is associated with progression toward type 2 diabetes and genetic variation in the ADIPOQ gene promoter. Diabetes Care. 2006; 29 ((7)) 1645-1650
- 41 Thamer C, Haap M. et al . Beta cell function, insulin resistance and plasma adiponectin concentrations are predictors for the change of postprandial glucose in non-diabetic subjects at risk for type 2 diabetes. Horm Metab Res. 2006; 38 ((3)) 178-182
- 42 Trajkovski M, Mziaut H. et al . Genes of type 2 diabetes in beta cells. Endocrinol Metab Clin North Am. 2006; 35 ((2)) 357-369
- 43 Wenying Y, Zhaojun Y. Obesity and hypertension as two anthropometric predictors for metabolic syndrome. Horm Metab Res. 2006; 38 ((7)) 469-470
- 44 Wilk JB, Myers RH. et al . Adrenergic receptor polymorphisms associated with resting heart rate: the HyperGEN Study. Ann Hum Genet. 2006; 70 ((Pt 5)) 566-573
- 45 Yuan X, Yamada K. et al . Beta 3-adrenergic receptor gene polymorphism is not a major genetic determinant of obesity and diabetes in Japanese general population. Diabetes Res Clin Pract. 1997; 37 ((1)) 1-7
Correspondence
Dr. P.E.H. Schwarz
Medical Faculty Carl-Gastav-Carus of the Technical University Dresden
Medical Clinic III
Building 10
Room 108
Fetscherstraße 74
01309 Dresden
Germany
Phone: +49/351/458 27 15
Fax: +49/351/458 73 19
Email: Peter.Schwarz@uniklinikum-dresden.de