The clinical and cardiometabolic effects of d3-growth hormone receptor polymorphism in acromegaly

Purpose Exon 3-deleted GH receptor variant (d3-GHR) is associated with increased responsiveness to exogenous GH. The aim of this study was to determine the effect of d3-GHR polymorphism on the GH/IGF-1 relationship, clinical parameters, and comorbidity in acromegalic patients. Methods The study included 118 acromegalic patients (61 female and 57 male; mean age: 50.3 +/- 12.2 years) and 108 healthy controls (94 female and 14 male: mean age: 41.1 +/- 11.1 years). The prevalence of GHR genotypes was evaluated via PCR. Results In all, 71 (60.2 %) patients had the fl/fl-GHR genotype, 40 (33.9 %) were heterozygous for the fl/d3-GHR genotype, and 7 (5.9 %) were homozygous for the d3/d3-GHR genotype. The prevalence of fl/fl-GHR, fl/d3-GHR, and d3/d3-GHR genotypes in the control group was 57.4, 29.6, and 13.0 %, respectively-similar prevalences as in the patient group. Patients that were heterozygous and homozygous for the d3 allele were subgrouped (d3-GHR subgroup), and were compared to those with the fl/fl-GHR genotype (fl/fl-GHR subgroup). Anthropometric measures, features of pituitary adenoma, and baseline GH and IGF-1 levels were similar in both subgroups. The prevalence of coronary artery disease, hypertension, hyperlipidemia, type 2 diabetes mellitus, and multinodular goiter did not differ between patient subgroups. In total, 24 (20.3 %) of the patients had cancer and the prevalence of cancer was similar in the d3-GHR (14.9 %) and fl/fl-GHR (23.9 %) subgroups (P = 0.23). More of the acromegalic patients that were d3 carriers had discordant GH and IGF-1 levels at baseline and post surgery, but the difference was not significant. A significant correlation between basal GH and IGF-1 levels was observed only in the patients with the fl/fl-GHR genotype (R-2 = 0.227, P<0.001). Conclusion The d3-GHR variant genotype did not have an effect on clinical features or comorbidity in acromegalic patients, but it might play a role in GH/IGF-1 level discordance in acromegaly.