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dc.contributor.advisorErbaş, Tomristr_TR
dc.contributor.authorÇınar, Neşetr_TR
dc.date.accessioned2015-10-14T10:03:35Z
dc.date.available2015-10-14T10:03:35Z
dc.date.issued2013tr_TR
dc.identifier.urihttp://hdl.handle.net/11655/919
dc.description.abstractBackground 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.tr_TR
dc.language.isoturtr_TR
dc.publisherTıp Fakültesitr_TR
dc.subjectAcromegalytr_TR
dc.titleD3-Büyüme Hormon Reseptör Polimorfizminin Akromegalı Hastalarında Klinik, Metabolik ve Kardiyovasküler Etkileritr_TR
dc.typeinfo:eu-repo/semantics/doctoralThesisen
dc.callno2013/684tr_TR
dc.contributor.departmentoldİç Hastalıkları Ana Bilim Dalıtr_TR
dc.description.ozetAmaç: Büyüme hormon reseptör (GHR) geninin sik görülen polimorfik varyantlarindan birisi ekzon 3 içeren "fl-GHR" ve içermeyen "d3-GHR" izoformlaridir. d3-GHR tasiyanlarda egzojen GH’nun indükledigi sinyal transdüksiyon hizi artmistir. Bu çalismada d3-GHR polimorfizminin akromegali hastalarinin klinik bulgulari ve komorbiditeleri ile iliskisini ortaya koymak amaçlanmistir. Yöntem: Çalismaya akromegali tanisi alan 118 hasta (61 K/57 E, ortalama yas: 50.3±12.2 yil) ve 108 saglikli kontrol (94 K/14 E, ortalama yas: 41.1±11.1 yil) dahil edildi. Genotip analizi periferik kan DNA’sinda PCR yöntemi ile yapildi. Hastalarin ve kontrollerin d3-GHR polimorfizm prevalanslari karsilastirildi. Akromegalik hastalarin demografik özellikleri, tani sirasindaki GH ve IGF-1 düzeyleri, adenomunun özellikleri, tedavi yöntemleri ve komorbiditeleri degerlendirildi. Bu parametreler ile d3-GHR polimorfizmi arasindaki iliski incelendi. Bulgular: Akromegalik hastalarin %60.2’sinde (n:71) fl/fl-GHR, %33.9’unda (n:40) d3-GHR heterozigot (fl/d3-GHR) ve %5.9’unda (n:7) d3-GHR homozigot (d3/d3- GHR) polimorfizmi saptandi. Kontrollerin ise %57.4’ünde (n:62) fl/fl-GHR, %29.6’sinda (n:32) fl/d3-GHR ve %13.0’ünde (n:14) d3/d3-GHR polimorfizmi bulundu. Polimorfizm sikliklari açisindan hasta ve kontrol grubu arasinda fark saptanmadi. Heterozigot ve homozigot d3 aleli tasiyan akromegalik hastalar birlikte gruplandirildi (d3-GHR) ve fl/fl-GHR grubu ile karsilastirildi. Demografik özellikler açisindan gruplar arasinda fark bulunmadi. Hastalarin tani aninda GH ve IGF-1 düzeyleri benzer bulundu. Adenom özellikleri (boyut, patolojik özellikleri ve kavernöz sinüs invazyon varligi) her iki grupta benzerdi. Tedavi yöntemleri gruplar arasinda farklilik göstermemekteydi. Koroner arter hastaligi, hipertansiyon, hiperlipidemi, Tip 2 diabetes mellitus prevalansi açisindan gruplar arasinda fark saptanmadi. Multinodüler guatr prevalansi gruplar arasinda benzer bulundu. Yirmi dört hastada kanser tespit edildi (%20.3) ve kanser riski üzerinde d3-GHR polimorfizminin bir etkisi gözlenmedi (d3-GHR, n:7; %14.9 vs. fl/fl-GHR, n:17; %23.9, p: 0.23). fl/fl-GHR grubunda tedavi öncesi GH ve IGF-1 düzeyleri arasinda ix anlamli iliski saptanirken (R²: 0.227, p<0.001), bu iliski d3-GHR grubunda (R²: 0.081, p:0.08) bulunmadi. Sonuç: Akromegalik hastalarda d3-GHR polimorfizm sikligi daha önce yapilan çalismalarla benzer bulunmustur. Bizim çalışmamız, d3-GHR genotipinin, akromegali hastalarının klinik bulguları ve komorbiditeleri üzerinde belirgin etkisi olmadigini destekler niteliktedir ancak bu polimorfizmin, GH ile IGF-1 disasosiasyonunda rol oynayabilecegi düsünülebilir.tr_TR
dc.subtypemedicineThesis


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