February 16, 2019
2 min read

GH receptor genotype may influence response to therapy in adults

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Among adults with growth hormone deficiency, the presence of a specific GH receptor allele influenced the level of response to GH therapy over 5 years, according to findings published in the Journal of Neuroendocrinology.

“In adult GH [deficiency], only a few studies have investigated the GH receptor polymorphism,” Laura De Marinis, MD, of the pituitary unit of the division of endocrinology at Catholic University School of Medicine in Rome, and colleagues wrote in the study background. “These observations demonstrate, in some cases, an increased response to [recombinant human] GH in patients carrying the [exon 3-deleted] GH [receptor] 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.”

Researchers analyzed data from 69 adults with GH deficiency before and during their treatment with GH therapy, using a low-dose protocol calculated on the basis of body weight and monitored via insulin-like growth factor I plasma assay (37 men; median age, 46 years). GH receptor genotype was determined from blood samples. Researchers used linear regression analysis to identify the most significant variables influencing variation in IGF-I levels.

Patients were stratified into three groups: homozygous carriers of the full-length GH receptor (flfl; n = 37), heterozygous carriers of the exon 3-deleted (d3) GH receptor (fld3; n = 23) and homozygous carriers of the d3 GH receptor (d3d3; n = 9). Researchers observed no clinical or anthropometric differences among genetic groups apart from a trend for higher BMI in d3d3 carriers.

After 6 months of GH therapy, all metabolic parameters remained unchanged across groups, according to researchers; however, at 12 months, the researchers observed an improvement in LDL cholesterol and body composition (decreased fat mass) in d3 carrier patients when compared with other genetic groups.

During 5-years of follow-up, HbA1c tended to increase across groups, reaching statistical significance in the flfl carriers (P < .05 vs. baseline and 6-month data), whereas LDL cholesterol and fat mass decreased in both d3 GH receptor carriers (P < .05 vs. baseline and 6-month data for both).

Researchers also observed that the presence of the d3d3 GH receptor was associated with an increase in IGF-I levels at 6 and 12 months of therapy (P < .05 vs. flfl and fld3 carriers), but not at 5 years. GH therapy also influenced systolic blood pressure after 12 months in d3 carriers vs. flfl carriers, according to researchers. At 5 years, researchers observed a change in LDL cholesterol among d3d3 carriers vs. flfl carriers.

“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 (only in d3d3 GH [receptor] group during long-term follow-up),” the researchers wrote. “The presence of the d3 GH [receptor] in homozygosity is associated with a significant IGF-I increment at 6 and 12 months of [recombinant human] GH replacement therapy.”

The researchers noted that other genetic factors may be involved with IGF-I response to GH therapy, and research in a larger cohort is needed.

“Nevertheless, we believe that our results could be of interest: They confirm that the d3 GH [receptor] genotype may influence some metabolic effects during short- and long-term follow-up of low-dose [recombinant human] GH replacement therapy and could be an independent determinant of the IGF-I increase during short-term follow-up in d3 homozygosity,” the researchers wrote. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.