Beta Adrenergic Receptor Variants In Human Hypertension

976 words - 4 pages

Hypertension is a complex trait, influenced by multiple environmental and genetic factors to ultimately determine blood pressure levels and the occurrence of various diseases [1]. Although numerous reports have provided evidence for the role of genes in the determination of blood pressure levels and hypertension, the identity of the contributing genes remains unclear [2]. Because there are diverse systems known to regulate blood pressure levels, one cannot limits particular genes encoding certain class of proteins could probably responsible in hypertension regulation. Convincing evidence for the identification of a true functional polymorphism for hypertension should come from diverse ...view middle of the document...

This review highlights the genetic variations in ADRB2 and its crucial role with hypertension.
FUNCTIONAL STUDIES OF ADRB2 VARIANTS
The human β2-adrenergic receptor is a G-protein-coupled receptor found in many tissue types and is a target for several β2-adrenoreceptor agonists and antagonists currently used in the treatment of various diseases. Individual variations in physiological responses, expression and function of the receptor, as well as individual differences in response to drugs that act on these receptors may relate to polymorphic variants of the receptor. In myocardium, β1 and β2 adrenergic receptors mediate inotropic and chronotropic responses to endogenous and exogenous adrenergic agents, while in vascular smooth muscle, β2-adrenergic receptors mediate vasodilatation in response to adrenergic agonists [9].
The human ADRB2 has seven transmembrane spanning domains, an extracellular N-terminus and an intracellular C-terminus, which is coupled to the stimulatory form of G protein (Gs). Specific amino acids within hydrophobic membrane-spanning regions of the ADRB2 function as targets for catecholamine ligand binding and activate adenylate cyclase activity and cyclic adenosine monophosphate (cAMP) synthesis by intracellular release of activated Gs [10]. cAMP serve as a second messenger in the signal transduction cascade by activating protein kinase A (PKA). The activation of PKA results in the cascade of protein phosphorylations, predominately enzymes, receptors, or channels which may be activated or deactivated upon phosphorylation. Through activation of cAMP-dependent protein kinase A and other signalling pathways, the ADRB2 regulates a number of metabolic and physiologic processes in various organs such as heart, lung and kidney [3].
The ADRB2 gene (MIM number: ID+109690, gene locus:5q32-34), which consists of a intronless block of 1,242 base pairs [4], has 9 single nucleotide polymorphism (SNPs) in the coding region of the ADRB2 gene and eight SNPs in the 5' upstream region of the ADRB2 gene identified. As shown in fig. 2, five variants in the coding region are silent (synonymous) SNPs, because...

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