D3 GH receptor polymorphism is not associated with IGF1 levels in untreated acromegaly

Abstract

Context: A discrepancy between serum GH and IGF1 concentrations is frequent in patients with acromegaly. Here, we examined whether the exon 3-deleted (d3) GH receptor (GHR) variant, which has been linked to increased responsiveness to GH treatment in short children, influences the GH/IGF1 relationship in patients with acromegaly. Objective: To study the possible influence of the GHR genotype on the GH/IGF1 relationship in untreated acromegalic patients. Design: GHR genotype analysis with retrospective clinical and biochemical data collection performed in a single third-reference medical center. Patients and methods: Clinical data were obtained from the medical records of 105 acromegalic patients who had GH and IGF1 assays in the same laboratory and who were genotyped for the full-length (fl) or d3-GHR alleles. Results: The distribution of GHR genotypes was 51% fl/fl, 30% fl/d3, and 19% d3/d3. Patients with d3/d3 genotype were younger than the patients in the other two groups (P!0.05). Baseline GH and IGF1 concentrations did not differ among the three groups. The linear correlation between GH and IGF1 concentrations was similar in the three genotypic groups. Conclusions: The exon 3 GHR genotype does not affect the GH/IGF1 relationship in untreated acromegalic patients with high circulating GH and IGF1 levels.

Impact of Successful Treatment of Acromegaly on Overnight Heart Rate Variability and Sleep Apnea

“…Serum IGF-1 levels were measured with a commercial kit, as previously reported (37). Age-adjusted IGF-1 values were calculated with age-specific reference ranges for our IGF-1 assay (IGF-1% ϭ patient's IGF-1/age specific upper limit ϫ 100, the age specific upper limit being the mean IGF-1 level normal for age and sex ϩ 2 SD).…”

MECHANISMS IN ENDOCRINOLOGY: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism

“…The number of patients with acromegaly examined varied from 19 to 186 among the reported series, with the prevalence of heterozygous d3/fl-GHR ranging from 13.3% to 57% and of d3-GHR homozygous from 0% to 22%. In one study, d3-GHR carriers were younger (61) and in another they had higher systolic blood pressure, fasting insulin, HOMA-IR and BMI (64). In the remaining, no clear differences in clinical parameters were observed between patients with or without d3-GHR allele.…”

“…To date, findings from 17 studies, which are summarized in Table 4, have not been consistent and the importance of the d3-GHR polymorphism in acromegaly management remains highly controversial (55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71). The number of patients with acromegaly examined varied from 19 to 186 among the reported series, with the prevalence of heterozygous d3/fl-GHR ranging from 13.3% to 57% and of d3-GHR homozygous from 0% to 22%.…”

The Exon-3 Deletion of the Growth Hormone Receptor (GHR) Gene Still Has a Limited Impact in Clinical Endocrinology

“…Thus, to document the effects of d3 genomic variation at the GHR locus upon the acromegalic phenotype would require the observation of a large number of patients relatively homogeneous for their degree of GH excess, age range, and disease duration, conditions that are rarely met. Studies in dozens of acromegalic patients suggested that the d3 allele was (15) or was not associated with differences in GH or IGF-I levels (16,17). A larger study suggested that the d3 allele was associated with a more morbid acromegalic clinical and biochemical picture (17).…”

“…Studies in dozens of acromegalic patients suggested that the d3 allele was (15) or was not associated with differences in GH or IGF-I levels (16,17). A larger study suggested that the d3 allele was associated with a more morbid acromegalic clinical and biochemical picture (17).…”