title: Beta(2)-adrenergic receptor gene polymorphism, age, and cardiovascular phenotypes.
abstract: Previous studies suggest that variants of the beta(2)-adrenergic receptor (ADRB2) may differently affect functional responses to adrenergic stimulation, thereby possibly modulating cardiovascular and metabolic phenotypes. We examined the hypothesis that G/R16 and Q/E27 polymorphism of ADRB2, or their haplotypes, may modulate blood pressure, cardiovascular structure, and function or metabolic cardiovascular risk factors in the general population. We examined a random sample of the general population (n=571; age, 35 to 64 years). Neither clinic nor 24-hour ambulatory blood pressure was significantly associated with ADRB2 genotypes in the overall population. Cardiac structure and function were also not influenced by ADRB2 polymorphism. After adjustment for potential confounders, association of the R16 allele with higher systolic blood pressure was observed in the subgroup of younger people (below age of 50 years). Haplotype analysis showed that higher blood pressure values were more specifically associated with the presence of R16-Q27. Younger people carrying the R16-Q27 haplotype also showed a trend toward lower heart rate, higher BMI, lower glycemia, and higher trygliceridemia, which is consistent with the hypothesis of a genetic predisposition to reduced cardiovascular and metabolic response to ADRB2 stimulation. This study does not provide evidence of a major role of ADRB2 gene variability in blood pressure modulation. However, association of ADRB2 polymorphism with cardiovascular and metabolic effects can be observed in younger subjects, before the development of age-related decline of ADRB2-mediated activity. Our study emphasizes the necessity of taking into account (patho)-physiological changes related to aging (in this case, decreased efficiency of ADRB2 signaling) when analyzing phenotypic effects of genetic variants.
authors.affiliation: Department of Medical and Surgical Sciences, University of Brescia, Italy. castell@master.cci.unibs.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Castellano
authors.forename: Federica
authors.initials: F
authors.lastname: Rossi
authors.forename: Mara
authors.initials: M
authors.lastname: Giacchè
authors.forename: Cristiano
authors.initials: C
authors.lastname: Perani
authors.forename: Francesca
authors.initials: F
authors.lastname: Rivadossi
authors.forename: Maria Lorenza
authors.initials: ML
authors.lastname: Muiesan
authors.forename: Massimo
authors.initials: M
authors.lastname: Salvetti
authors.forename: Marina
authors.initials: M
authors.lastname: Beschi
authors.forename: Damiano
authors.initials: D
authors.lastname: Rizzoni
authors.forename: Enrico
authors.initials: E
authors.lastname: Agabiti-Rosei
mesh_terms: D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000502:physiology*; D002319:Cardiovascular System / Q000000981:diagnostic imaging / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D018343:Receptors, Adrenergic, beta-2