A genetic polymorphism of the alpha2-adrenergic receptor increases autonomic responses to stress.

@article{Finley2004AGP,
  title={A genetic polymorphism of the alpha2-adrenergic receptor increases autonomic responses to stress.},
  author={J Clayton Finley and Michael O'Leary and Derin C. Wester and Steven Mackenzie and Neil Shepard and Stephen Farrow and Warren E. Lockette},
  journal={Journal of applied physiology},
  year={2004},
  volume={96 6},
  pages={
          2231-9
        }
}
We hypothesized that individual differences in autonomic responses to psychological, physiological, or environmental stresses are inherited, and exaggerated autonomic responsiveness may represent an intermediate phenotype that can contribute to the development of essential hypertension in humans over time. alpha(2)-Adrenergic receptors (alpha(2)-ARs), encoded by a gene on chromosome 10, are found in the central nervous system and also mediate release of norepinephrine from the presynaptic nerve… 

Figures from this paper

Alpha-adrenoceptor gene variants and autonomic nervous system function in a young healthy Japanese population

The α1A-AR and α2C-AR genetic variations influence sympatho-vagal balance even in young and healthy normotensive states, which could be postulated to constitute an intermediate phenotype for future pathological episodes of various ANS dysfunction-related diseases.

Sympathetic nervous system, genes and human essential hypertension.

The physiology of the SNS and its influence on cardiovascular and renal mechanisms of BP regulation are described and a thorough review of the role of genetic variability of various SNS genes in relation to the development of BP and essential hypertension follows.

Genetic variations of α(2)-adrenergic receptors illuminate the diversity of receptor functions.

Resting sympathetic nerve activity is related to age, sex and arterial pressure but not to α2-adrenergic receptor subtype

Variant alleles of three α2-adrenergic receptor subtypes were not related to resting muscle sympathetic nerve hyperactivity, indicating that their functional differences shown in vitro are not reflected in sympathetic activity in man.

Complex haplotypes derived from noncoding polymorphisms of the intronless alpha2A-adrenergic gene diversify receptor expression.

Signaling by this virtually ubiquitous receptor is under major genetic influence, which may be the basis for highly divergent phenotypes in complex diseases such as systemic and pulmonary hypertension, heart failure, diabetes, and obesity.

A gene-environment interaction model of stress-induced hypertension

The elucidation of the gene-environment interaction model of stress-induced essential hypertension will improve the understanding of the contribution of stress to the development of essential hypertension.

Overexpression of Alpha2A-Adrenergic Receptors Contributes to Type 2 Diabetes

Using congenic strains from the diabetic Goto-Kakizaki rat, a 1.4-megabase genomic locus was identified that was linked to impaired insulin granule docking at the plasma membrane and reduced β cell exocytosis and a single-nucleotide polymorphism in the human ADRA2A gene for which risk allele carriers exhibited overexpression of alpha(2A)AR, reduced insulin secretion, and increased type 2 diabetes risk.

Adrenergic signaling polymorphisms and their impact on cardiovascular disease.

  • G. Dorn
  • Biology, Medicine
    Physiological reviews
  • 2010
The current state of laboratory and clinical evidence that adrenergic pathway polymorphisms can affect cardiovascular pathophysiology is comprehensively reviewed and compared, with a goal of placing these data in the broad context of potential clinical applicability.

Familial orthostatic tachycardia

Genetic testing can reveal molecular mechanisms of disease and provide an additional strategy for diagnosis and treatment of heterogeneous patient populations such as postural tachycardia syndrome.
...

References

SHOWING 1-10 OF 39 REFERENCES

Alpha 2-adrenergic receptor gene polymorphism and hypertension in blacks.

Expression of altered α2‐adrenergic phenotypic traits in normotensive humans at genetic risk of hereditary (essential) hypertension

It is concluded that heterogeneous, bimodally distributed hemodynamic and biochemical responses to α2-adrenergic blockade in subjects with positive family histories of hypertension suggest a discrete subgroup with early expression of perhaps Mendian traits associated with hypertension itself may be associated with later phenotypes.

Effect of the α2‐Adrenergic Antagonist Yohimbine on Orthostatic Tolerance

Because this agent increases forearm blood flow, yohimbine might be useful in treating the orthostatic hypotension and ischemic vascular disease that results from the autonomic insufficiency common in patients with diabetes mellitus.

The Sympathetic System in Hypertension: State‐of‐the‐Art Review

Increased renal afferent nerve activity may provoke an increase in sympathetic activity and provide a link between natriuretic factors and the sympathetic nervous system in hypertension.

The sympathetic nervous system in hypertension.

  • F. Abboud
  • Biology, Medicine
    Clinical and experimental hypertension. Part A, Theory and practice
  • 1984
Several studies in various animal models and in humans are described to support the notion that the mosaic concept in hypertension may be embodied in a dual theory that includes a vascular muscle defect coupled with excessive sympathetic drive both of which may be of genetic or acquired origin.

Polymorphism in the &bgr;1-Adrenergic Receptor Gene and Hypertension

The data suggest that individuals homozygous for the Arg389 allele of the &bgr;1-adrenergic receptor gene are at increased risk to develop hypertension.

The sympathetic skin response in peripheral autonomic failure — evaluation in pure autonomic failure, pure cholinergic dysautonomia and dopamine-beta-hydroxylase deficiency

The sympathetic skin response (SSR) detects changes in the electrical potential in the skin in response to physiological and electrical stimuli and, therefore, may indicate the integrity of

Sympathetic Reactivity During a Yohimbine Challenge Test in Essential Hypertension

A yohimbine challenge test can identify patients with pressor hyperresponsiveness and can distinguish patients withPressorhyperresponsiveness due to excessive sympathoadrenal reactivity from patients with enhanced postsynaptic responsiveness to endogenous NE.