D3-Büyüme Hormon Reseptör Polimorfizminin Akromegalı Hastalarında Klinik, Metabolik ve Kardiyovasküler Etkileri

Abstract

Background and aim: A common polymorphic variant of the growth hormone receptor (GHR) consists of genomic deletion of exon 3 (d3-GHR) or full-length genotype (fl-GHR). d3-GHR is associated with increased responsiveness to signal transduction of the exogenous GH. The aim of this study was to determine the relationship between the d3-GHR polymorphism and clinical parameters and comorbidities of the acromegalic patients. Methods: 118 acromegalic patients (61F/57M, age: 50.3±12.2 yrs) and 108 healthy controls (94F/ 14M, age: 41.1±11.1 yrs) were included in the study. Genotype analysis was performed by PCR. The prevalence of d3-GHR polymorphism was compared in patients and controls. Demographic features, GH, IGF-1 levels at diagnosis, features of the adenoma, treatment modalities, and comorbidities of the patients were evaluated. Impact of d3-GHR polymorphism on these parameters was evaluated. Results: Seventy-one patients (60.2%) were fl/fl-GHR, 40 patients (33.9%) were heterozygotes (fl/d3-GHR) and seven patients (5.9%) were homozygotes (d3/d3- GHR) for genomic deletion of exon 3. The prevalence of fl/fl-GHR, fl/d3-GHR and d3/d3-GHR in controls were 57.4%, 29.6% and 13.0% respectively. No significant difference was observed in the distribution of these polymorphisms among the groups. Heterozygotes and homozygotes for the d3 allele were considered together (d3-GHR) in the patients and compared with fl/fl-GHR group. d3-GHR and fl/fl- GHR patients showed similar anthropometric measures. Baseline GH and IGF-1 levels did not differ between the groups. Both groups showed similar adenoma features (size and the presence of cavernous sinus invasion). Moreover, treatment modalities did not show any difference. The prevalence of comorbidities such as coronary artery disease, hypertension, hyperlipidemia, Type 2 diabetes mellitus and multinodular goiter were similar in both groups. There were 24 cancer patients (20.3%) and there was no significant difference in the prevalence of cancer among d3-GHR and fl/fl-GHR patients (n:7, 14.9 % vs n:17, 23.9%; p: 0.23). A significant correlation between basal GH and IGF-1 levels (R²: 0.227, p<0.001) was observed in fl/fl-GHR group whereas no significant association was found in d3- GHR group (R²: 0.081, p: 0.08). xi Conclusion: The distribution of the genotype for d3GHR in this study was similar to previous studies in acromegaly. Our study supports that the genotype of d3GHR variant seems to have no impact on clinical features and comorbidities of acromegalic patients, but may play role in the GH/IGF-1 disassociation in acromegaly.