Alpha2B adrenergic receptor 301-303 deletion polymorphism and vascular alpha2 adrenergic receptor response.

Muszkat M, Sofowora GG, Xie HG, Wood AJ, Stein CM
Pharmacogenet Genomics. 2005 15 (1): 23-8

PMID: 15864122 · DOI:10.1097/01213011-200501000-00004

Postsynaptic alpha2B adrenergic receptors (ARs) mediate vasoconstriction. There is more than 1000-fold variability in vascular sensitivity to an alpha2-AR agonist. Genetic variability may contribute to such interindividual differences in sensitivity. A 301-303 deletion (del) polymorphism has been identified in the coding region of the alpha2B-AR gene and has functional effects in vitro. Thus, we examined the hypothesis that the del301-303 polymorphism contributes to variability in vascular alpha2-AR responses in vivo. Healthy subjects were recruited based on their alpha2B-AR genotype. Their vascular sensitivity was determined using a linear variable differential transformer following the infusion of increasing doses (range 0.01-1000 ng/min) of the alpha2-AR agonist, dexmedetomidine, into a dorsal hand vein. The dose that produced 50% (ED50) of maximum venoconstriction (Emax) was determined for each subject. Vascular response was compared among the three genotypes. Forty-nine subjects were studied [28 wild-type wt/wt, 13 wt/del, 8 del/del]. There was no difference in dexmedetomidine ED50 and Emax among the alpha2B-AR del301-303 genotypes. The ED50 was 1.39 ng/min [95% confidence interval (CI) 0.03-63.0 ng/min] in wt/wt subjects, 1.63 ng/min (95% CI 0.01-177.8 ng/min) in wt/del and 2.37 ng/min (95% CI 0.17-33.7 ng/min) in del/del (P=0.80). The average Emax was 75.4+/-14.9% in wt/wt, 75.7+/-21.3% in wt/del and 82.2+/-12.9% in del/del subjects (P=0.26). These findings suggest that the del301-303 polymorphism does not contribute significantly to interindividual in vivo variability in response to alpha2-AR activation in the hand vein.

MeSH Terms (14)

Adrenergic alpha-Agonists Adult Dexmedetomidine Female Gene Deletion Genetic Variation Genotype Homozygote Humans Male Pharmacogenetics Polymorphism, Genetic Receptors, Adrenergic, alpha-2 Veins

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