Abstract
In this study, the effects of polymorphisms of the β2 and β3 adrenergic receptor genes on the occurrence of dyslipidemia and diabetes mellitus in hypertensive patients treated with β-blockers (atenolol or metoprolol) were evaluated. Patients who gave written informed consent were asked to return for blood sampling for estimation of serum glucose, total cholesterol, HDL, triglycerides and for genotype determination. Genotyping analysis was performed by PCR-RFLP assay. In patients bearing β2AR Glu27 or the β3AR Arg64 variant there was a larger occurrence of hypertriglyceridemia, alone or in combination with elevated cholesterol levels. Furthermore, the β2AR Glu27 variant significantly associates with hypetriglyceridemia in a cumulative fashion. The risk to develop this side effect after β-blockade was four-fold higher in patients homozygous for the β2AR Glu27 variant as compared to β2AR27Gln allele. This result allows the identification of patients at high risk to develop metabolic complications to chronic β-blockade treatment.
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References
Frishman WH . Beta-adrenergic receptor blockers. Adverse effects and drug interactions. Hypertension 1988; 11: II21–9.
Green SA, Turki J, Innis M, Liggett SB . Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994; 33: 9414–9419.
Green SA, Turki J, Hall IP, Liggett SB . Implications of genetic variability of human beta 2-adrenergic receptor structure. Pulm Pharmacol 1995; 8: 1–10.
Dishy V, Sofowara GG, Xie HG, Kim RB, Byrne DW, Stein CM et al. The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med 2001; 345: 1030–1035.
Strosberg AD . Structure, function, and regulation of adrenergic receptors. Protein Sci 1993; 2: 1198–1209.
Revelli JP, Preitner F, Samec S, Muniesa P, Kuehne F, Boss O et al. Targeted gene disruption reveals a leptin-independent role for the mouse beta3-adrenoceptor in the regulation of body composition. J Clin Invest 1997; 100: 1098–1106.
Susulic VS, Frederich RC, Lawitts J, Tozzo E, Kahn BB, Harper ME et al. Targeted disruption of the beta 3-adrenergic receptor gene. J Biol Chem 1995; 270: 29483–29492.
Shima Y, Tsukada T, Nakanishi K, Ohta H . Association of the Trp64Arg mutation of the beta3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects. Clin Chim Acta 1998; 274: 167–176.
Widen E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC et al. Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med 1995; 333: 348–351.
Ehrenborg E, Skogsberg J, Ruotolo G, Large V, Eriksson P, Arner P et al. The Q/E27 polymorphism in the beta2-adrenoceptor gene is associated with increased body weight and dyslipoproteinaemia involving triglyceride-rich lipoproteins. J Intern Med 2000; 247: 651–656.
Malczewska-Malec M, Wybranska I, Leszczynska-Golabek I, Niedbal S, Kwasniak M, Hartwich J 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: CR225–CR234.
Ryden M, Hoffstedt J, Eriksson P, Bringman S, Arner P . The Arg 389 Gly beta1-adrenergic receptor gene polymorphism and human fat cell lipolysis. Int J Obes Relat Metab Disord 2001; 25: 1599–1603.
World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 1999; 17: 151–183.
Iaccarino G, Lanni F, Cipolletta E, Trimarco V, Izzo R, Iovino GL et al. The Glu27 allele of the beta2 adrenergic receptor increases the risk of cardiac hypertrophy in hypertension. J Hypertens 2004; 22: 2117–2122.
Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26 (Suppl 1): S5–S20.
Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III) Final Report. Rationale for Intervention. Circulation 2002; 106: 3163–3223.
Iwamoto N, Ogawa Y, Kajihara S, Hisatomi A, Yasutake T, Yoshimura T et al. Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clin Chim Acta 2001; 314: 85–91.
Hagstrom-Toft E, Enoksson S, Moberg E, Bolinder J, Arner P . Beta-adrenergic regulation of lipolysis and blood flow in human skeletal muscle in vivo. Am J Physiol 1998; 275: E909–E916.
Holm C, Belfrage P, Fredrikson G . Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue. Biochem Biophys Res Commun 1987; 148: 99–105.
Abraham WT, Iyengar S . Practical considerations for switching beta-blockers in heart failure patients. Rev Cardiovasc Med 2004; 5 (Suppl 1): S36–S44.
Manraj M, Francke S, Hebe A, Ramjuttun US, Froguel P . Genetic and environmental nature of the insulin resistance syndrome in Indo-Mauritian subjects with premature coronary heart disease: contribution of beta3-adrenoreceptor gene polymorphism and beta blockers on triglyceride and HDL concentrations. Diabetologia 2001; 44: 115–122.
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This work was supported by a grant from the Italian Ministry of Instruction University and Research (MIUR).
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Iaccarino, G., Trimarco, V., Lanni, F. et al. β-Blockade and increased dyslipidemia in patients bearing Glu27 variant of β2 adrenergic receptor gene. Pharmacogenomics J 5, 292–297 (2005). https://doi.org/10.1038/sj.tpj.6500324
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DOI: https://doi.org/10.1038/sj.tpj.6500324
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