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Published in: Diabetologia 3/2007

01-03-2007 | Article

Studies of the associations between functional β2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects

Authors: A. P. Gjesing, G. Andersen, K. S. Burgdorf, K. Borch-Johnsen, T. Jørgensen, T. Hansen, O. Pedersen

Published in: Diabetologia | Issue 3/2007

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Abstract

Aims/hypothesis

Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the β2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results.

Materials and methods

We investigated both of these variants in 7,808 unrelated, middle-aged white people for their association with obesity in a case–control study, quantitative trait analysis and meta-analysis. Moreover, both variants were investigated for their potential influence on measures of hypertension and type 2 diabetes by case–control and quantitative trait analyses.

Results

The present study did not find consistent evidence for an association of these β2-adrenergic receptor variants with obesity or hypertension; neither did the quantitative trait analyses show any effect of the variants on obesity-related traits. However, both the Gly allele of the Arg16Gly variant and the Glu allele of the Gln27Glu variant showed nominal association with systolic blood pressure. Furthermore, there was a nominal association of the Arg16 allele frequency and genotype distribution with type 2 diabetes; however, no influence on quantitative biochemical phenotypes related to type 2 diabetes was found. A nominal association of the Arg/Gly genotype with the metabolic syndrome was also observed (p = 0.003). Logistic regression analyses provided no evidence of a synergistic or an additive effect of these variants on obesity, hypertension or diabetes.

Conclusions/interpretation

After studying 7,808 middle-aged white subjects, we were unable to demonstrate any consistent associations between two common amino acid polymorphisms of the β2-adrenergic receptor and obesity, hypertension or type 2 diabetes.
Literature
1.
go back to reference Reihsaus E, Innis M, MacIntyre N, Liggett SB (1993) Mutations in the gene encoding for the β2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 8:334–339PubMed Reihsaus E, Innis M, MacIntyre N, Liggett SB (1993) Mutations in the gene encoding for the β2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 8:334–339PubMed
2.
go back to reference Large V, Hellström L, Reynisdottir S et al (1997) Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. J Clin Invest 100:3005–3013PubMedCrossRef Large V, Hellström L, Reynisdottir S et al (1997) Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. J Clin Invest 100:3005–3013PubMedCrossRef
3.
go back to reference Green SA, Turki J, Innis M, Liggett SB (1994) Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33:9414–9419PubMedCrossRef Green SA, Turki J, Innis M, Liggett SB (1994) Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33:9414–9419PubMedCrossRef
4.
go back to reference Oberkofler H, Esterbauer H, Hell E, Krempler F, Patsch W (2000) The Gln27Glu polymorphism in the β2-adrenergic receptor gene is not associated with morbid obesity in Austrian women. Int J Obes 24:388–390CrossRef Oberkofler H, Esterbauer H, Hell E, Krempler F, Patsch W (2000) The Gln27Glu polymorphism in the β2-adrenergic receptor gene is not associated with morbid obesity in Austrian women. Int J Obes 24:388–390CrossRef
5.
go back to reference Meirhaeghe A, Helbecque N, Cottel D, Amouyel P (2000) Impact of polymorphisms of the human β 2 -adrenoceptor gene on obesity in a French population. Int J Obes 24:382–387CrossRef Meirhaeghe A, Helbecque N, Cottel D, Amouyel P (2000) Impact of polymorphisms of the human β 2 -adrenoceptor gene on obesity in a French population. Int J Obes 24:382–387CrossRef
6.
go back to reference Iwamoto N, Ogawa Y, Kajihara S et al (2001) Gln27Glu β2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clin Chim Acta 314:85–91PubMedCrossRef Iwamoto N, Ogawa Y, Kajihara S et al (2001) Gln27Glu β2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clin Chim Acta 314:85–91PubMedCrossRef
7.
go back to reference Tafel J, Branscheid I, Skwarna B (2004) Variants in the human β1-, β2- and β3-adrenergic receptor genes are not associated with morbid obesity in children and adolescents. Diabetes Obes Metab 6:452–455PubMedCrossRef Tafel J, Branscheid I, Skwarna B (2004) Variants in the human β1-, β2- and β3-adrenergic receptor genes are not associated with morbid obesity in children and adolescents. Diabetes Obes Metab 6:452–455PubMedCrossRef
8.
go back to reference Kim SH, Kim DJ, Seo IA et al (2002) Significance of β2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects. Metabolism 51:833–837PubMedCrossRef Kim SH, Kim DJ, Seo IA et al (2002) Significance of β2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects. Metabolism 51:833–837PubMedCrossRef
9.
go back to reference Castellano M, Rossi F, Gicchè M et al (2003) β2-Adrenergic receptor gene polymorphism, age, and cardiovascular phenotypes. Hypertension 41:361–367PubMedCrossRef Castellano M, Rossi F, Gicchè M et al (2003) β2-Adrenergic receptor gene polymorphism, age, and cardiovascular phenotypes. Hypertension 41:361–367PubMedCrossRef
10.
go back to reference Pereira AC, Floriano MS, Mota GFA et al (2003) β2 Adrenoceptor functional gene variants, obesity, and blood pressure level interactions in the general population. Hypertension 42:685–692PubMedCrossRef Pereira AC, Floriano MS, Mota GFA et al (2003) β2 Adrenoceptor functional gene variants, obesity, and blood pressure level interactions in the general population. Hypertension 42:685–692PubMedCrossRef
11.
go back to reference Ellsworth DL, Coady SA, Chen W et al (2002) Influence of the β2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study. Int J Obes 26:928–937CrossRef Ellsworth DL, Coady SA, Chen W et al (2002) Influence of the β2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study. Int J Obes 26:928–937CrossRef
12.
go back to reference Kato N, Sugiyama T, Morita H et al (2001) Association analysis of β2-adrenergic receptor polymorphisms with hypertension in Japanese. Hypertension 37:286–292PubMed Kato N, Sugiyama T, Morita H et al (2001) Association analysis of β2-adrenergic receptor polymorphisms with hypertension in Japanese. Hypertension 37:286–292PubMed
13.
go back to reference Lin RCY, Ericsson JO, Benjafield AV, Morris BJ (2001) Association of β2-adrenoceptor Gln27Glu variant with body weight but not hypertension. Am J Hypertens 14:1201–1204PubMedCrossRef Lin RCY, Ericsson JO, Benjafield AV, Morris BJ (2001) Association of β2-adrenoceptor Gln27Glu variant with body weight but not hypertension. Am J Hypertens 14:1201–1204PubMedCrossRef
14.
go back to reference Mori Y, Kim-Motoyama H, Ito Y et al (1999) The Gln27Glu β2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men. Biochem Biophys Res Commun 258:138–140PubMedCrossRef Mori Y, Kim-Motoyama H, Ito Y et al (1999) The Gln27Glu β2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men. Biochem Biophys Res Commun 258:138–140PubMedCrossRef
15.
go back to reference Busjahn A, Li G, Faulhaber H et al (2000) β-2 Adrenergic receptor gene variations, blood pressure, and heart size in normal twins. Hypertension 35:555–560PubMed Busjahn A, Li G, Faulhaber H et al (2000) β-2 Adrenergic receptor gene variations, blood pressure, and heart size in normal twins. Hypertension 35:555–560PubMed
16.
go back to reference Ishiyama-Shigemoto S, Yamada K, Yuan X, Ichikawa F, Nonaka K (1999) Association of polymorphisms in the β2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia 42:98–101PubMedCrossRef Ishiyama-Shigemoto S, Yamada K, Yuan X, Ichikawa F, Nonaka K (1999) Association of polymorphisms in the β2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia 42:98–101PubMedCrossRef
17.
go back to reference Sánchez JLG, Proenza AM, Larrad MTM et al (2003) The glutamine 27 glutamic acid polymorphism of the β2-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 59:476–481CrossRef Sánchez JLG, Proenza AM, Larrad MTM et al (2003) The glutamine 27 glutamic acid polymorphism of the β2-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 59:476–481CrossRef
18.
go back to reference Carlsson M, Orho-Melander M, Hedenbro J, Groop LC (2001) Common variants in the β2-(Gln27Glu) and β3-(Trp64Arg)-adrenoceptor genes are associated with elevated serum NEFA concentration and type II diabetes. Diabetologia 44:629–636PubMedCrossRef Carlsson M, Orho-Melander M, Hedenbro J, Groop LC (2001) Common variants in the β2-(Gln27Glu) and β3-(Trp64Arg)-adrenoceptor genes are associated with elevated serum NEFA concentration and type II diabetes. Diabetologia 44:629–636PubMedCrossRef
19.
go back to reference Jørgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glümer C, Pisinger C (2003) A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99 (1). Eur J Cardiovasc Prev Rehabil 10:377–386PubMedCrossRef Jørgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glümer C, Pisinger C (2003) A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99 (1). Eur J Cardiovasc Prev Rehabil 10:377–386PubMedCrossRef
20.
go back to reference Alberti KGMM, Zimmett PZ (1999) for a WHO consultation. Definition, diagnosis and classification of diabetes mellitus and its complications; Part 1: diagnosis and classification of diabetes mellitus. World Health Organization, Geneva Alberti KGMM, Zimmett PZ (1999) for a WHO consultation. Definition, diagnosis and classification of diabetes mellitus and its complications; Part 1: diagnosis and classification of diabetes mellitus. World Health Organization, Geneva
21.
go back to reference National Cholesterol Education Program (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285:2486–2497CrossRef National Cholesterol Education Program (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285:2486–2497CrossRef
22.
go back to reference Andersen G, Overgaard J, Albrechtsen A et al (2006) Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes. Diabetologia 49:75–82PubMedCrossRef Andersen G, Overgaard J, Albrechtsen A et al (2006) Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes. Diabetologia 49:75–82PubMedCrossRef
23.
go back to reference Buetow KH, Edmonson M, MacDonald R et al (2001) High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci USA 98:581–584PubMedCrossRef Buetow KH, Edmonson M, MacDonald R et al (2001) High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci USA 98:581–584PubMedCrossRef
24.
go back to reference Echwald SM, Sørensen TIA, Tybjærg-Hansen A, Andersen T, Pedersen O (1998) Gln27Glu variant of the human β2-adrenoceptor gene is not associated with early-onset obesity in Danish men. Diabetes 47:1657–1658PubMed Echwald SM, Sørensen TIA, Tybjærg-Hansen A, Andersen T, Pedersen O (1998) Gln27Glu variant of the human β2-adrenoceptor gene is not associated with early-onset obesity in Danish men. Diabetes 47:1657–1658PubMed
25.
go back to reference Kortner B, Wolf A, Wendt D, Beisiegel U, Evans D (1999) Lack of association between a human β-2 adrenoceptor gene polymorphism (gln27glu) and morbid obesity. Int J Obes 23:1099–1100CrossRef Kortner B, Wolf A, Wendt D, Beisiegel U, Evans D (1999) Lack of association between a human β-2 adrenoceptor gene polymorphism (gln27glu) and morbid obesity. Int J Obes 23:1099–1100CrossRef
26.
go back to reference Corbálan MS, Marti A, Forga L, Martinez-González MA, Martinez JA (2002) β2-Adrenergic receptor mutation and abdominal obesity risk: effect modification by gender and HDL-cholesterol. Eur J Nutr 41:114–118PubMedCrossRef Corbálan MS, Marti A, Forga L, Martinez-González MA, Martinez JA (2002) β2-Adrenergic receptor mutation and abdominal obesity risk: effect modification by gender and HDL-cholesterol. Eur J Nutr 41:114–118PubMedCrossRef
27.
go back to reference Hellström L, Large V, Reynisdottir S, Wahrenberg H, Arner P (1999) The different effects of a Gln27Glu β2-adrenoceptor gene polymorphism on obesity in males and females. J Intern Med 245:253–259PubMedCrossRef Hellström L, Large V, Reynisdottir S, Wahrenberg H, Arner P (1999) The different effects of a Gln27Glu β2-adrenoceptor gene polymorphism on obesity in males and females. J Intern Med 245:253–259PubMedCrossRef
28.
go back to reference Dallongeville J, Helbecque N, Cottel D, Amouyel P, Meirhaeghe A (2003) The Gly16→Arg16 and Gln27→Glu27 polymorphism of β2-adrenergic receptor are associated with metabolic syndrome in men. J Clin Endocrinol Metab 88:4862–4866PubMedCrossRef Dallongeville J, Helbecque N, Cottel D, Amouyel P, Meirhaeghe A (2003) The Gly16→Arg16 and Gln27→Glu27 polymorphism of β2-adrenergic receptor are associated with metabolic syndrome in men. J Clin Endocrinol Metab 88:4862–4866PubMedCrossRef
Metadata
Title
Studies of the associations between functional β2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects
Authors
A. P. Gjesing
G. Andersen
K. S. Burgdorf
K. Borch-Johnsen
T. Jørgensen
T. Hansen
O. Pedersen
Publication date
01-03-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 3/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0578-8

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