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
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Email: Peter.Schwarz@uniklinikum-dresden.de