Adrenergic receptor genes are candidate genes for obesity and type 2 diabetes because they regulate lipid mobilization. An association has been reported between the frequently occurring Gly27Gln polymorphism of the β2-adrenergic receptor (B2ADR) gene with obesity (1,2) and triglycerides (3) in nondiabetic subjects.

We studied 542 unrelated type 2 diabetic subjects to assess the possible relationship of the Glu27Gln polymorphism of the B2ADR gene with obesity, as well as with plasma lipids. The Medical Ethics Committee of the University Medical Center Utrecht approved the study, and all participants signed an informed consent. The Glu27Gln polymorphism was examined by a modification of a PCR/restriction fragment–length polymorphism–based method (3) in duplicate and included sequence-verified controls.

After exclusion of PCR failures, genotypes were obtained for 502 type 2 diabetic patients. Subjects were subdivided according to three genotype groups: 109 subjects were Gln27Gln, 225 were Glu27Gln, and 168 were Glu27Glu. ANOVA of age at diagnosis of type 2 diabetes (61 ± 10, 60 ± 9, and 61 ± 9 years for the Gln27Gln, Glu27Gln, and Glu27Glu genotype groups, respectively), BMI (27.2 ± 3.8, 27.9 ± 4.4, and 28.2 ± 4.0 kg/m2), HbA1c (7.2 ± 1.4, 7.4 ± 1.3, and 7.2 ± 1.2%; normal values <6.1%), plasma cholesterol (5.3 ± 1.2, 5.3 ± 1.0, and 5.3 ± 1.0 mmol/l), plasma HDL cholesterol (1.2 ± 0.3, 1.1 ± 0.3, and 1.2 ± 0.3 mmol/l), and plasma triglycerides (1.8 ± 1.1, 1.9 ± 0.9, and 1.9 ± 0.1 mmol/l) showed no statistically significant differences (all P > 0.26). After exclusion of the insulin-treated subjects, the differences were also not statistically significant. We also found no significant differences for men or women separately.

We conclude that, at least in our cohort of subjects with type 2 diabetes, the Glu27Gln polymorphism of the β2-adrenergic receptor has no important effect on BMI, age at diagnosis of diabetes, metabolic control, or plasma lipids.

This work was supported by the Dutch Diabetes Research Foundation (Amersfoort, the Netherlands, DFN grant 97.114 to C.W. and T.W.v.H.).

1
Large V, Hellstrom L, Reynisdottir S, Lonnqvist F, Eriksson P, Lannfelt L, Arner P: Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function.
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Ehrenborg E, Skogsberg J, Ruotolo G, Large V, Eriksson P, Arner P, Hamstra A: The Q/E27 polymorphism in the beta2-adrenoceptor gene is associated with increased body weight and dyslipoproteinaemia involving triglyceride-rich lipoproteins.
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Rosmond R, Ukkola O, Chagnon M, Bouchard C, Bjorntorp P: Polymorphisms of the beta2-adrenergic receptor gene (ADBR2) in relation to cardiovascular risk factors in men.
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Address correspondence to Timon W. van Haeften, MD, Department of Internal Medicine, G 02.228, P.O. Box 85500, NL 3508 GA Utrecht, The Netherlands. E-mail: [email protected]

DIABETES CARE
2003