Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly.

Abstract

CONTEXT:

Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture.

OBJECTIVE:

Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment.

SETTING:

The study was conducted at a specialized clinic at a tertiary care hospital.

DESIGN, PATIENTS, AND METHODS:

We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR.

MAIN OUTCOME MEASURES:

We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics.

RESULTS:

Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58).

CONCLUSIONS:

The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy.

• Authors: Moisés Mercado, Baldomero González, Carolina Sandoval, Yoshua Esquenazi, Fernando Mier, Guadalupe Vargas, Ana Laura Espinosa de los Monteros, Ernesto Sosa
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 93 Issue 9 Pg. 3411-5 (Sep 2008) ISSN: 0021-972X [Print] United States
• PMID: 18611972 (Publication Type: Journal Article)

Chemical References

• Receptors, Somatotropin
• Insulin-Like Growth Factor I

Topics

• Acromegaly (genetics)
• Adult
• Aged
• Aged, 80 and over
• Exons
• Female
• Gene Deletion
• Gene Frequency
• Genotype
• Humans
• Insulin-Like Growth Factor I (analysis)
• Male
• Middle Aged
• Receptors, Somatotropin (genetics)
• Retrospective Studies