Mechanisms in endocrinology: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism

• Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system. As the first genetic variant to potentially influence the individual response to rhGH therapy in children with growth disorders, polymorphism in the GH receptor (GHR) has attracted a great interest as a target for pharmacogenetics. Studies have been conducted to compare the functional and molecular effects of the full-length GHR (fl-GHR) isoform with the exon 3 deleted (d3-GHR) isoform in children and adults treated with rhGH therapy. Additionally, the impact of the GHR polymorphism has been investigated in relation to the clinical status and response to medical treatment in acromegaly, especially to the GHR antagonist drug pegvisomant. We have performed a narrative review of the studies performed to date on the association of GHR polymorphism with rhGH response in children and adults, and its potential influence in the medical management of acromegaly. In addition, data from studies on the general population and in other chronic diseases examining a role of this genetic variant in the regulation of growth and metabolism are summarized. © 2017 European Society of Endocrinology.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

growth hormone receptor

human growth hormone

isoprotein

pegvisomant

peptide fragment

recombinant protein

acromegaly

adult

adverse effects

agonists

analogs and derivatives

antagonists and inhibitors

chemically induced

child

deficiency

drug resistance

exon

gene deletion

genetic polymorphism

genetics

Growth Disorders

hormone substitution

human

metabolism

pharmacogenetic variant

Exons

Hormone Replacement Therapy

Humans

Peptide Fragments

Pharmacogenomic Variants

Polymorphism

Genetic

Protein Isoforms

Receptors

Somatotropin

Recombinant Proteins

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)