Beta-2-adrenergic receptor polymorphisms and changes in lipids induced by metoprolol.
Polymorphisms Arg(16)Gly and Gln(27)Glu of the gene of adrenoreceptor beta(2)(ADRB2) are associated with altered sympathetic responses. This study evaluated the relationship between these polymorphisms and changes in lipids induced by metoprolol in hypertensive patients. 105 adults were enrolled. After serum lipid levels and genotype had been determined, metoprolol was administered orally. Genotyping was performed using a mini-sequencing technique. Allelic and genotypic frequencies were: Arg(16) (49.5%); Gly(16) (50.5%); Gln(27) (89%); Glu(27) (11%); Arg(16)Arg (28.6%); Arg(16)Gly (41.9%); Gly(16)Gly (29.5%); Gln(27)Gln (81%); Gln(27)Glu (16.1%), and Glu(27)Glu (2.9%). Ninety patients concluded the study. There were no significant differences between the demographic, pharmacological and biochemical variables evaluated, grouped by their genotype in positions 16 and 27 of the ADRB2 gene. We did not find differences in lipid profiles in the whole group, but when we compared these profiles within each genotypic subgroup, we found that total cholesterol diminished (p = 0.03) in the patients with the native Gln(27)Gln genotype, whereas in the Gln(27)Glu heterozygous triglycerides increased (p = 0.025). We only found 3 patients homozygous for Glu(27)Glu and 2 of them were treated with diet and antidyslipidemic drugs. These results suggest that the polymorphism of codon 27 constitutes the target of the changes in lipids induced by beta-adrenergic receptor antagonists.
Isaza
Carlos A
CA
Laboratorio de Genética Médica, Universidad Tecnológica de Pereira, Pereira, Colombia.
Henao
Julieta
J
Sánchez
Julio C
JC
Porras
Gloria L
GL
Cardona
J
J
Bedoya
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D000319:Adrenergic beta-Antagonists; D008055:Lipids; D018343:Receptors, Adrenergic, beta-2; D008790:Metoprolol