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The Gly¹⁶Arg¹⁶ and Gln²⁷Glu²⁷ Polymorphisms of ß₂-Adrenergic Receptor Are Associated with Metabolic Syndrome in Men

Institut National de la Santé et de la Recherche Médicale, U-508, Institut Pasteur de Lille (J.D., N.H., D.C., P.A., A.M.), and Faculté de Médecine, Université Lille II (P.A.), 59019 Lille Cedex, France

Address all correspondence and requests for reprints to: Dr. Jean Dallongeville, Institut National de la Santé et de la Recherche Médicale, U-508, 1 rue du Prof. Calmette, Institut Pasteur de Lille, 59019 Lille Cedex, France. E-mail: jean.dallongeville{at}pasteur-lille.fr.

Endogenous catecholamines contribute to regulation of adipose tissue lipolysis, glucose homeostasis, and vascular tone. The goal of the present study was to assess the association between the Gly¹⁶Arg¹⁶ and Gln²⁷Glu²⁷ polymorphisms of the ß₂-adrenergic receptor and metabolic syndrome. Participants were recruited in a population survey and included 1195 men and women. Metabolic syndrome was defined according to National Cholesterol Education Program Adult Treatment Panel III guidelines. There were 276 patients with metabolic syndrome and 872 controls. The Gly¹⁶Arg¹⁶ (P < 0.005) and Gln²⁷Glu²⁷ (P < 0.04) polymorphisms were associated with metabolic syndrome in men, but not in women. In multivariate analyses adjusting for age, physical activity, smoking habits, alcohol consumption, and body mass index, the odds ratio of metabolic syndrome was 1.83 (95% confidence interval, 1.10–3.05) and 2.43 (95% confidence interval, 1.19–4.95) in men bearing the Gly¹⁶/Arg¹⁶ and Arg¹⁶/Arg¹⁶ genotypes, respectively. Similarly, the odds ratios of metabolic syndrome were 0.99 (95% confidence interval, 0.50–1.93) and 1.67 (95% confidence interval, 0.84–3.33) in men bearing the Gln²⁷/Glu²⁷ and Gln²⁷/Gln²⁷ genotypes, respectively. Because both variants were in linkage disequilibrium, a haplotype analysis was performed. There was no evidence of any statistically significant association between ß₂-adrenergic receptor haplotypes and metabolic syndrome. In conclusion, these data suggest that the Arg¹⁶ and Gln²⁷ variants of the ß₂-adrenergic receptor gene contribute to metabolic syndrome susceptibility in men.

The WHO-MONICA population study developed in the North of France was supported by unrestricted grants from the Conseil Régional du Nord-Pas de Calais, ONIVINS, Parke-Davies Laboratory, the Mutuelle Générale de l’Education Nationale, Groupe Fournier, the Réseau National de Santé Publique, the Direction Générale de la Santé, Institut National de la Santé et de la Recherche Médicale, the Institut Pasteur de Lille and the Unité d’Evaluation du Centre Hospitalier et Universitaire de Lille.

Abbreviations: BAR, ß-Adrenergic receptor; BMI, body mass index; HDL, high-density lipoprotein; NCEP, National Cholesterol Education Program; OR, odds ratio; SNP, single nucleotide polymorphism.

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