β-2 Adrenoceptor genetic variation is associated with genetic predisposition to essential hypertension: The Bergen Blood Pressure Study

Abstract

We tested the hypothesis that genetic variation in the beta-2 adrenoceptor gene is associated with a genetic predisposition to hypertension. Offspring of two hypertensive parents were compared with offspring of two normotensive parents. The subjects were participants of the Bergen Blood Pressure Study, where couples were recruited in 1963 to 1964 and re-examined in 1990. We studied offspring of those couples in which both partners were either hypertensive or normotensive in both examinations. Twenty-three hypertensive and 22 normotensive families met the inclusion criteria. DNA samples from the first born of hypertensive family-history offspring and normotensive family-history offspring were analyzed. We used multiplex sequencing and specifically examined the promoter and the N-terminal portion of the beta-2 adrenoceptor gene. We found four genetic variants: at position -47, a C-->T substitution in the 5' leader cistron causing an Arg-->Cys exchange, at -20, a T-->C substitution, at +46 an A-->G substitution leading to an Arg16-->Gly exchange, and at +79, a C-->G substitution leading to a Gln27-->Glu exchange. The frequency of the Arg16 allele was significantly higher in the hypertensive family-history offspring compared to normotensive family-history offspring (58% vs. 28% P < 0.011). We constructed haplotypes for the four intragenic variants and found significant linkage dysequilibrium. In particular, the 5' leader cistron mutant with the wild type alleles at the other loci was significantly more frequent in offspring of hypertensive parents, compared to offspring of normotensive parents. We also performed a relative risk analysis comparing the Gly/Gly, Arg/Gly, and Arg/Arg alleles, which implicated the Arg-containing allele. Finally, we analyzed the effect of genotype on blood pressure in the offspring. We found a significant step-wise effect for all four polymorphisms examined. Our data suggest that the Arg variant of the Arg-->Gly exchange is associated with parental hypertension and higher blood pressure values in this northern European population.

Impact of polymorphisms of the human β2-adrenoceptor gene on obesity in a French population

“…As previously described, 7,8,10,28 we showed that the two polymorphisms were in complete linkage disequilibrium, the rare Arg16 allele being associated with the frequent Gln27 allele. When the impacts of these two polymorphisms were studied simultaneously, only the Gln27Glu polymorphism modi®ed the risk of developing obesity.…”

“…Reihsaus and collaborators detected nine polymorphisms in the human b 2 -adrenoceptor (BAR-2) gene in normal and asthmatic subjects. 3 The impacts of two common polymorphisms, the Gly16Arg and Gln27Glu substitutions, have been explored in several diseases, such as asthma, 4 ± 6 parental hypertension 7 and obesity. 8 ± 12 Large and colleagues described the impacts of these two polymorphisms in a group of 140 Swedish women with body mass index between 17.8 and 60.0 kgam 2 .…”

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.…”

Interacción entre los polimorfismos del receptor ß1 y ß2 adrenérgico como predictor de riesgo de insuficiencia cardiaca crónica

“…Los efectos in vivo de estos polimorfismos fueron inicialmente asociados con una mayor susceptibilidad al asma bronquial [18][19][20][21] . El polimorfismo ß 2 -RA Arg16Gly también ha sido asociado con hipertensión arterial [22][23][24][25] y aumentos de las presiones diastólica y sistólica 26,27 . La variante ß 2 -RA Ile164 es un alelo muy poco frecuente que disminuye la afinidad del receptor a su agonista 28 y ha sido asociado con la progresión de la IC 29 .…”