Genetic polymorphism of the alpha 2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans.
It is likely that a number of independent heritable traits, each encoded by a singular gene, contribute to pathologic elevations in blood pressure in humans. Genetic polymorphisms of individual genes may result in intermediate phenotypes which, by themselves, do not raise blood pressure, but, coupled with environmental or epistatic forces, contribute to the prevalence of human hypertension. The gene for the alpha 2-adrenergic receptor encoded by chromosome 10 (C10 A2AR) is polymorphic, and Southern blotting with a cDNA probe following restriction enzyme digest of this gene results in fragments of either 6.3 kb or 6.7 kb in size. We reported an association between homozygosity for the 6.3 kb allele and hypertension in blacks. Blacks with hypertension also have an increased risk for thrombotic stroke, increased baroreceptor sensitivity, and decreased sodium excretion. We noted that the C10 A2AR, which modulates norepinephrine release in blood-pressure-regulating regions of the brain, is also expressed on platelets and in the kidney. We postulated that functional changes associated with the C10 A2AR gene polymorphism could be responsible for increased baroreceptor sensitivity, epinephrine-mediated platelet aggregation, and decreased sodium excretion in some individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
Freeman
K
K
Department of Medicine, University of Michigan Medical School, Ann Arbor 48109, USA.
Farrow
S
S
Schmaier
A
A
Freedman
R
R
Schork
T
T
Lockette
W
W
D000483:Alleles; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D010974:Platelet Aggregation / Q000502:physiology*; D011110:Polymorphism, Genetic; D011311:Pressoreceptors / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D012964:Sodium / Q000652:urine*
D018076:DNA, Complementary; D018341:Receptors, Adrenergic, alpha-2; D012964:Sodium