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PRESENCE OF SPECIFIC GENETIC ALLELE INFLUENCES RESPONSE TO GROWTH HORMONE THERAPY


Written by Dr. Welsh, Article reviewed and edited by Dr. Fine M.D..
Published on 15 July 2021

For some people, human growth hormone (HGH) replacement therapy works wonders and for other people, it can take a long time to see any results. We know that everyone is different and everyone reacts differently to medicines, procedures and therapy, but in terms of growth hormone therapy, we now know why some people respond better than others. Not surprisingly, the answer lies in our genes, or genetics.

Growth Hormone Genotype Influences Response to Therapy for Adults

For adults that are suffering from adult-onset growth hormone deficiency, what determines how well they respond to therapy, or the level of response over the course of five years, is partly determined by the presence or absence of a specific growth hormone receptor allele in their genes, according to recent research published in the Journal of Neuroendocrinology. An allele is one of two or more alternative forms of a gene that are found at the same place (locus) on the chromosome. Alleles can occur in pairs and different alleles can affect the expression of a particular trait. In this case, the presence of a certain allele influences an adult’s response to growth hormone therapy.

An author of the study, Laura De Marinis, MD, from the Catholic University School of Medicine in Rome, stated, “In adult GH [deficiency], only a few studies have investigated the GH receptor polymorphism. These observations demonstrate, in some cases, an increased response to GH in patients carrying the GH allele, but with conflicting and not-conclusive data. Moreover, in some studies, an improvement in lipid metabolism or a worsening of glucose tolerance has been observed.” Hmm, it appears that the presence of these alleles makes things pretty complicated, according to scientists.

By “polymorphism,” De Marinis is describing the fact that there is more than one allele that is occupying that location on the gene. An easy way to understand how this works, is a simple example. On our genes, there are multiple locations of specific genetic code, called alleles. If a rat has an allele that codes for grey hair, then that rat will have grey-colored hair. Another rat might have a totally different allele that happens to code for white hair – therefore, that rat has white hair. The same goes for the alleles in this instance. If a certain type of allele is present at that location on the gene, the better  or worse a patient will respond to growth hormone (GH) therapy.

Determination of Genetic Influence on Response to GH Therapy

In the study, 69 adults with growth hormone deficiency were studied, both before and after treatment. The therapy used a low-dose protocol (typical for growth hormone replacement therapy treating adult GH deficiency) that was based on the patient’s body weight and monitored via insulin-like growth factor-1 (IGF-1) blood tests. Whether the patient had the GH receptor genotype of interest or not was determined from blood samples as well.

The patients were split up into three separate groups: homozygous carriers of the full-length GH receptor; heterozygous carriers of the exon 3-deleted (d3) GH receptor; and homozygous carriers of the d3 GH receptor.

After six full months of low-dose growth hormone therapy, all metabolic parameters remained the same between groups. However, by 12 months, there were significant differences observed. In the d3 carrier patients, there was significant improvement in LDL cholesterol and body composition, as observed by decreased fat mass.

There was five years of follow-up with the patients in this study. Over the course of these five years, HbA1c increased across all groups (the higher the HbA1c level, the more likely you have diabetes) but LDL cholesterol and fat mass decreased in both d3 GH receptor carriers.

In addition, the patients that had the d3d3 GH receptor demonstrated higher IGF-1 levels at 6 and 12 months of therapy, but not by five years.

Presence of d3 Allele Related to More Effective Response to GH Replacement Therapy

Based on their results, the researchers stated, “The presence of the d3 GH [receptor] appears to be related to a more effective response in terms of reduction of LDL, fat mass and improvement in blood pressure. The presence of the d3 GH [receptor] in homozygosity is associated with a significant IGF-1 increment at 6 and 12 months of GH replacement therapy.”

However, there are probably other genetic factors involved in IGF-1 response to growth hormone therapy and more research is needed, of course.

The scientists believe that their results, “confirm that the d3 GH [receptor] genotype may influence some metabolic effects during short- and long-term follow-up of low dose GH replacement therapy…”

What is Adult-Onset Growth Hormone Deficiency?

Both children and adults can suffer from a growth hormone deficiency, when the body is not producing enough growth hormone. Children need it in order to grow to their ideal height and adults need it in order to maintain cellular regeneration, metabolism and muscle mass. In recent years, it has been confirmed that adults can experience a deficiency of growth hormone as they age that is greatly influenced by lifestyle, diet and exercise.

Symptoms of deficiency include chronic fatigue, unexplained weight gain (especially in the belly area), low libido or sex drive, erectile dysfunction, low bone mineral density, low muscle mass leading to sarcopenia and thinning skin/hair. A deficiency is determined via a blood test, testing for the patient’s level of IGF-1 in the blood stream, a metabolite of growth hormone.

Most of the time, if an adult is suffering from a deficiency, they’ll need to undergo a low-dose growth hormone replacement therapy program, just like the patients in this study. The goal is to find the dose that provides just the right amount of growth hormone – not too much and not too low. The only option at this time, for treatment, is HGH injections and sermorelin acetate injections. Pills or sprays will not work for treatment – the hormones must be injected subcutaneously.

If you suspect that you are suffering from a growth hormone deficiency, it’s best to get your blood tested as soon as possible. This is something simple to do and once done, you’ll have the peace of mind knowing whether you really have a hormone imbalance or not. Contact our clinic to discuss the process of a comprehensive hormone panel and how hormone replacement therapy works. We offer free consultations! Call us today!

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