D3-büyüme hormon reseptör polimorfizminin akromegali hastalarında klinik, metabolik ve kardiyovasküler etkileri
The clinical and cardiometabolic effects of D3 growth hormone receptor polymorphism in acromegaly
- Tez No: 339470
- Danışmanlar: PROF. DR. TOMRİS ERBAŞ
- Tez Türü: Tıpta Yan Dal Uzmanlık
- Konular: Endokrinoloji ve Metabolizma Hastalıkları, Endocrinology and Metabolic Diseases
- Anahtar Kelimeler: Akromegali, Büyüme hormonu, Diabetes mellitus-tip 2, Koroner hastalık, Neoplazmlar, Polimorfizm-genetik, İnsülin benzeri büyüme faktörü I, Acromegaly, Growth hormone, Diabetes mellitus-type 2, Coronary disease, Neoplasms, Polymorphism-genetic, Insulin like growth factor I
- Yıl: 2013
- Dil: Türkçe
- Üniversite: Hacettepe Üniversitesi
- Enstitü: Tıp Fakültesi
- Ana Bilim Dalı: Endokrinoloji ve Metabolizma Bilim Dalı
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: Belirtilmemiş.
Özet
Amaç: Büyüme hormon reseptör (GHR) geninin sık görülen polimorfik varyantlarından birisi ekzon 3 içeren
Özet (Çeviri)
Background and aim: A common polymorphic variant of the growth hormone receptor (GHR) consists of genomic deletion of exon 3 (d3GHR) or full-length genotype (flGHR). D3GHR is associated with increased responsiveness to signal transduction of the exogenous GH. The aim of this study was to determine the relationship between the d3GHR 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 d3GHR polymorphism was compared in patients and controls. Demographic features, comorbidities of the patients, GH, IGF-1 levels at diagnosis, features of the adenoma and treatment modalities were evaluated. Results: Seventy-one patients (60.2%) were fl/flGHR, 40 patients (33.9%) were heterozygotes (fl/d3GHR) and 7 patients (5.9%) were homozygotes (d3/d3GHR) for genomic deletion of exon 3. The prevalence of fl/fl GHR, fl/d3GHR and d3/d3GHR in controls were 57.4%, 29.6% and 13% 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 (d3GHR) in the patients and compared with fl/flGHR group. D3GHR and fl/flGHR patients showed similar anthropometric measures. Baseline GH and IGF-1 levels did not differ between the groups. A significant correlation between GH and IGF-1 levels (r:0.498, p<0.001) was observed in fl/flGHR group whereas no significant association was found in d3GHR group (r:0.283, p=0.08). Both groups showed similar adenoma features (size and the presence of cavernous sinus invasion). The prevalence of comorbidities such as coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus and multinodular guatr were similar in both groups. There were 23 cancer patients (19.5%) and there was no significant difference in the prevalence of cancer among d3GHR and fl/flGHR patients (n:6, 12.8% vs n:17, 23.9%, respectively). The prevalence of renal cortical cyst and nefrolithiasis were also equally distributed. Moreover, treatment modalities did not show any difference. Conclusion: The distribution of the genotype for d3GHR in this study was similar to previous studies in acromegaly. Controversial results have been reported in studies about the effect of D3GHR polymorphism in acromegaly that more favourable metabolic phenotype was found in d3GHR patients in a study while significantly higher BMI and HOMA-IR values were observed in d3/d3GHR group in another study. 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.
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