Polymorphisms of the β<sub>2</sub>‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men

Rosmond, Roland; Ukkola, Olavi; Chagnon, Monique; Bouchard, Claude; Björntorp, Per

doi:10.1046/j.1365-2796.2000.00721.x

Cited by 55 publications

(31 citation statements)

References 26 publications

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“…In accordance with other studies that found higher triglyceridaemia in subjects bearing the Glu allele, 13,19,42,43 plasma triglycerides (TG) remained higher in our Glu27Glu group than in the Gln27Gln group throughout the study. On the other hand, the only measured hormone that significantly differed between groups was insulin, which was higher in the Glu27Glu group.…”

Section: Adrb2 Polymorphism and Exercise In Obese Womensupporting

confidence: 93%

Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women

Macho-Azcarate

Martí

González³

et al. 2002

Int J Obes

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BACKGROUND:The Glu27Glu genotype in the beta-2-adrenergic receptor (ADRB2) is associated with fat mass, body mass index and obesity in females. In our population, we previously found an association of higher body mass index (BMI) among women who reported more physical activity and carried the Glu27 allele as compared to non carriers with the same level of activity. OBJECTIVE: To examine the lipid metabolism differences, both at rest and during submaximal exercise in ADRB2 Glu27Glu vs Gln27Gln obese women. SUBJECTS: Eight obese women with the Glu27Glu genotype (age, 43 AE 5 y; body mass index (BMI), 31.7 AE 0.9 kg=m 2 ; percentage fat mass, 42.0 AE 1.3; WHR, 0.83 AE 0.02; and VO 2max , 21.6 AE 0.9 ml=kg=min) were compared with seven obese women with the Gln27Gln genotype (age, 43 AE 5 y; BMI, 33.9 AE 1.3 kg=m 2 ; percentage fat mass, 41.6 AE 1.2; WHR, 0.83 AE 0.02; and VO 2max , 20.6 AE 0.8 ml=kg=min). MEASUREMENTS: The ADRB2 polymorphism was identified by PCR-RFLP. Respiratory quotient was determined by indirect calorimetry at baseline, during 1 h of walking on a treadmill and 1 h after the exercise. Plasma triglycerides, glycerol, FFA, hydroxybutyrate, glucose and lactate were assayed by spectrophotometric methods. Insulin, leptin and progesterone were measured by radioimmunoassay. Adrenaline and noradrenaline were quantified by high performance liquid chromatography. RESULTS: The ADRB2 Glu27Glu subjects had lower plasma glycerol (P ¼ 0.047) and lower hydroxybutyrate (P ¼ 0.001) throughout the study than the Gln27Gln group. Plasma triglycerides (P ¼ 0.001), lactate (P < 0.05) and serum insulin (P < 0.05) remained higher in the Glu27Glu group vs the Gln27Gln group. The respiratory quotient (RQ) was higher in the Glu27Glu obese women along the study (P ¼ 0.046), and fat oxidation was significantly lower in this group during the recovery (P ¼ 0.048). The other variables did not differ statistically between groups. CONCLUSION: These data suggest that both lipolysis and fat oxidation promoted by an acute submaximal exercise intervention could be blunted in the polymorphic ADRB2 Glu27Glu group of our female obese population.

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Section: Adrb2 Polymorphism and Exercise In Obese Womensupporting

confidence: 93%

Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women

Macho-Azcarate

Martí

González³

et al. 2002

Int J Obes

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“…An Arg16Gly variant was found to be associated with a significant 1.8-fold increase risk of hypertension. 234 Confirmatory results for this variant have been reported in other populations 235,236 as well as a negative study. 237 Attenuation of the vasodilatory response in humans with the Gly16 allele provides biological plausibility.…”

Section: ␣-Adducin (Add1)supporting

confidence: 73%

Genetics of hypertension

Hopkins

Hunt

2003

Genetics in Medicine

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Hypertension is the most prevalent cardiovascular disorder. In the 1999 to 2000 NHANES survey, the prevalence of hypertension progressively increased from 7.2% in those aged 18 to 39 to 30.1% in 40 to 59 year olds and 65.4% in those 60 and older. 1 Risk of both coronary atherosclerosis and stroke increase exponentially as blood pressure rises (see Fig. 1). 2 Although the relative risk for stroke increases more rapidly than coronary disease, at any pressure, the absolute risk for coronary disease is considerably greater than for stroke. An insight into this finding comes from autopsy studies that show that the carotid and intracerebral vascular beds are relatively protected from atherosclerosis as compared to the coronary circulation, particularly at lower blood pressures (see Fig. 2). 3,4 Probably the major means whereby hypertension accelerates atherosclerosis is through pressure-driven convection of LDL and other atherogenic particles into the arterial intima. 5-8 Indeed, without at least arterial pressures, atherosclerosis does not exist in the vascular tree 9 even in patients with homozygous familial hypercholesterolemia. 10,11 Increased turbulence (a rare occurrence in the human circulatory system) does not increase atherosclerosis. Rather, higher sheer stress is a strong stimulus for release of nitric oxide that locally decreases risk of atherosclerosis. Focal areas of low sheer stress are at inherently increased risk of atherosclerotic disease (such as the coronary arteries where flow stops during each systole). 12 Interestingly, in most studies, stroke risk has been affected little by serum total cholesterol, 13,14 although some recent studies identify clear associated risk. 15 At least some association with all standard cardiovascular risk factors should be expected, not only because thromboembolic stroke may be caused by carotid tree atherosclerosis, but because aortic plaques have been strongly implicated as an embolic source for ischemic stroke. 16 -18 Hypertension is not just a risk factor for atherosclerosis. High blood pressure can have direct adverse effects on arteries, arterioles, and the heart, resulting in potentially severe consequences beyond the more common manifestations of myocardial infarction and atherothrombotic stroke. Even modestly elevated blood pressure is a major risk factor for congestive heart failure. 19,20 Hypertension is a major contributor to left ventricular hypertrophy, a major risk factor for sudden death independent of other risk factors. 21,22 Hypertension can lead progressively to arterial and arteriolar hypertrophy, arteriosclerosis and arteriolosclerosis, and with very high pressures to fibrinoid change and fibrinoid necrosis in arterioles. These latter changes can result in lumen compromise of arterioles resulting in lacunar stroke, Charcot-Bouchard aneurysms, glomerulosclerosis and nephrosclerosis, and ultimately malignant hypertension in the kidney and retinal ischemia and blindness. Risk of intracerebral hemorrhage is increased 33-fold at stage 3 or higher pre...

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“…The β2AR polymorphisms accounted for ∼2% of the observed variation in blood pressure (Bray et al 2000). While results of some groups confirmed the association between the 16Gly allele and blood pressure (Kotanko et al 1997;Rosmond et al 2000;Gratze et al 1999), others found opposite effects, i.e., an association between the 16Arg allele and hypertension (Busjahn et al 2000;Bengtsson et al 2001a,b;Timmermann et al 1998) or no effects at all (Herrmann et al 2002;Kato et al 2001;Xie et al 2000; for a recent meta-analysis see Hahntow et al 2006). Again, differing inclusion of haplotypes, variations in ethnicities and different study designs may contribute to these sobering results.…”

Section: Genetic Variants In β-Adrenoceptor Genesmentioning

confidence: 98%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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Polymorphisms of the β₂‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men

Cited by 55 publications

References 26 publications

Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women

Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women

Genetics of hypertension

Genetics of arterial hypertension and hypotension

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Polymorphisms of the β2‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men

Cited by 55 publications

References 26 publications

Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women

Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women

Genetics of hypertension

Genetics of arterial hypertension and hypotension

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Product

Resources

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Polymorphisms of the β₂‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men