2-Adrenergic receptor polymorphisms at codon 16, cardiovascular phenotypes and essential hypertension in whites and African Americans

Abstract

Beta2-adrenergic receptors (beta2-AR) contribute to cardiovascular regulation by influencing several functions and previous studies suggest that a decreased function of the beta2-AR may be involved in essential hypertension. Beta2-AR are polymorphic and certain polymorphisms of these receptors are of functional importance. We focus here on the Arg16-->Gly16 beta2-AR polymorphism, which shows enhanced agonist-promoted downregulation of the receptor and which, in two recent studies, yielded opposite results in terms of association with essential hypertension: an increased frequency of the Gly16 variant in African-Caribbean hypertensives and of the Arg16 variant in offspring of Norwegian white hypertensive parents. In the current study, we genotyped 243 subjects, including both African-American and white individuals, for codon 16 polymorphism and assessed blood pressure and cardiovascular function using impedance cardiography and pressor sensitivity to phenylephrine. We found similar patterns of cardiovascular function and expression of hypertension with the two genotypes of codon 16. There was no statistically significant difference in the overall allelic distribution of the two genotypes: among African-Americans, 51% of the hypertensives and 50% of the normotensives carried the Arg16 allele, whereas among the white subjects 40% of the hypertensives and 47% of the normotensives were carriers of the Arg16 allele. Although we observed a statistically significant increase in the Arg16/Gly16 heterozygotes in the African-American population, the Gly16 allele was not significantly increased in the African-Americans compared to whites. These findings indicate that the codon 16 polymorphisms are not associated with hypertension in a mixed American study population nor do they appear to substantially impact on a variety of hemodynamic variables.

A46G and C79G polymorphisms in the β2-adrenergic receptor gene (ADRB2) and essential hypertension risk: a meta-analysis

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]27,28 Of the 19 eligible articles, the study of Gu et al 28 was replaced by their earlier report, 10 as these two articles reported the same data. Wu et al 5 provided data on two Chinese minorities, the Hani and Yi, residents of the remote rural area of Yunnan, China.…”

“…29 The population of the two minorities was also grouped in to Asian. 30 Tang et al, 27 Herrmann et al 18 and Xie et al 14 provided data on two ethnicities: Caucasian American and AfricanAmerican. The genotyping data of the normotensive controls in the population Caucasian-American in Tang et al 27 (P HWE ¼0.048), and the African-American control subjects studied in Herrmann et al 18 (P HWE ¼0.027) deviated from HWE.…”

“…30 Tang et al, 27 Herrmann et al 18 and Xie et al 14 provided data on two ethnicities: Caucasian American and AfricanAmerican. The genotyping data of the normotensive controls in the population Caucasian-American in Tang et al 27 (P HWE ¼0.048), and the African-American control subjects studied in Herrmann et al 18 (P HWE ¼0.027) deviated from HWE. The same occurred with the data provided in Mo et al 11 (P HWE o0.001), Ge et al 10 (P HWE ¼0.040) and The random-effects model was used to pool the results, as the between-study heterogeneity was significant.…”

“…Other studies have been unable to replicate these findings. [12][13][14][15][16][17][18][19][20] Therefore, in spite of the large number of previous reports about the association between these two polymorphisms and hypertension, the conclusion remains unclear. To clarify the effect of A46G and C79G polymorphisms on the risk of hypertension, we conducted a meta-analysis from all eligible case-control studies published to date.…”

Genetic polymorphisms and heart failure

“…92 However, other studies have failed to detect any association between the Arg16Gly and Gln27Glu polymorphisms and cardiac dimensions. [95][96][97] These studies did not investigate the role of the Thr164Ile variant.…”