Association Analysis of β ₂ -Adrenergic Receptor Polymorphisms With Hypertension in Japanese

Abstract

Abstract-Significant evidence has been provided for the pathophysiological involvement of the ␤ 2 -adrenergic receptor (ADRB2) in hypertension. Among ADRB2 polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and Gln27Glu, and a promoter variant, T-47C, are considered functionally important. In particular, Arg16Gly was shown to be associated with hypertension in black and white subjects. To investigate the relevance of ADRB2 polymorphisms to hypertension, we undertook an extensive association study in a Japanese population. An association was tested in 2 ways. First, a case-control study was conducted in 842 hypertensive and 633 normotensive subjects. In addition to the overall comparison between case and control groups, each was stratified by body mass index and compared with an independent panel of 525 diabetic subjects. Second, ANOVA and multivariate analyses were performed to test the significance of an association between ADRB2 genotype and the level of blood pressure within the entire population except for 395 subjects who had been under treatment for hypertension. Although no significant association was observed for Arg16Gly and T-47C, 2 analytical methods indicated a marginal association (Pϭ0.01 to 0.04) between the Glu27 variant and lower blood pressure levels. Given such a normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99) reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no apparent confounding influences of obesity and diabetes on the postulated association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to confer principal genetic susceptibility for hypertension in the Japanese population. However, further investigation is warranted to clarify the relevance of ADRB2 polymorphisms to blood pressure regulation. (Hypertension. 2001;37:286-292.)

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

“…The present case-control study examining the effect of the Arg16Gly and Gln27Glu variants on hypertension was negative, which is in accord with previous reports [10,12]. An Italian study observed a higher prevalence of hypertension among carriers of the Arg allele when individuals below 50 years of age were analysed independently [9].…”

“…Investigators have examined the effect of the two variants combined; however, no clear picture has emerged [9,12]. In the present logistic regression analysis for the two variants combined there was no indication of an effect of the variants on hypertension.…”

“…The same ambiguity is observed when the two variants are examined in relation to hypertension [9,10,[12][13][14][15] and type 2 diabetes [2,5,9,14,[16][17][18].…”

Genetics of arterial hypertension and hypotension

“…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.…”

.BETA.2- and .BETA.3-Adrenoceptor Polymorphisms Relate to Subsequent Weight Gain and Blood Pressure Elevation in Obese Normotensive Individuals

“…Two polymorphisms in the β2-adrenergic receptors (arginine/glycine substitution, Arg16Gly; and glutamine/ glutamate substitution, Gln27Glu) of the β2-adrenoceptor gene were studied (6,7). One polymorphism (tryptophan/ arginine substitution, Trp64Arg) of the β3-adrenoceptor gene was also studied (10).…”