Author/Editor		Zavratnik, Andrej
Title		Vpliv polimorfizmov gena za estrogenski receptor alfa na učinke raloksifena
Translated title		Influence of estrogen receptor alpha gene polymorphisms on raloxifene effects
Type		članek
Source		In: Čokolič M, editor. Novosti v osteologiji: monografija vabljenih predavanj II. osteoloških dnevov, Maribor, 9.-10. oktober 2009. Maribor: Univerzitetni klinični center,
Publication year		2009
Volume		str. 178-86
Language		slo
Abstract		Background: The selective estrogen receptor modulator, raloxifene, exerts a part of its actions through the estrogen receptor alpha (ESRI) activation. We explored if polymorphisms of the ESR1 modify the effects of six months raloxifene treatment on vascular function and lipids and twelve months raloxifene treatment on osteoporosis parameters. Patients and methods: Prospective clinical trial. A total of 53 postmenopausal women, mean age 59.7+/-6.2, finished the trial. The PvulI, Xbal, and P325P polymorphisms of the ESR1 gene were analyzed. ln all subjects endothelium dependent flow mediated dilatation (FMD), cell adhesion molecules (CAM) - lCAM-1, YCAM-1 and E-selectin were measured before and after six months of raloxifene treatment. Specific alkaline phosphatase (BSAP), osteocalcin (OC), C-telopeptide cross-links of type I collagen (CTX) and serum lipids were determined before, after 6, and 12 months of the raloxifene treatment. The bone mineral density (BMD) of lumbar spine and left hip by dual energy X-ray absorptiometry (DXA) were assessed at the beginning and after 12 months of the treatment. Results: After raloxifene treatment, the FMD was significantly greater in subjects with xx genotype of Xbal polymorphism compared to xx (p=0.03), and borderline greater when compared to xx genotype (p=0.053). When comparing women with non-CC genotype to CC-genotype of P325P polymorphism the total cholesterol levels (p=0.015 and p=0.037) and LDL cholesterol levels (p=0.008 and p=0.042) were significantly lower after 6 and 12 months and reduction of the total cholesterol as significantly bigger (p=0.045) after 6 months of raloxifene treatment. There were no other significant effects of ESR1 polymorphisms on raloxifene treatment observed. There was no relation between the ESR1 polymorphisms and studied parameters at baseline. (Abs. trunc. at 2000 ch.)
Summary		Izhodišča: Raloksifen je selektivni modulator estrogenskih receptorjev, ki vsaj del svojih učinkov izraža preko aktivacije estrogenskega receptorja alfa (ESRl). Raziskovali smo vpliv polimorfizmov (ESR1) na endotelijsko funkcijo med šest mesečnim zdravljenjem z raloksifenom in vpliv na krvne maščobe ter kazalce za osteoporozo med dvanajst mesečnim zdravljenjem z raloksifenom. Bolniki in metode: Prospektivna klinična raziskava. Raziskavo je zaključilo 53 pomenopavzalnih žensk, povprečne starosti 59,7+/-6,2 leta. Določali smo PvuII, Xbal in P325P polimorfizme v ESR1 genu. Pred zdravljenjem in po šestih mesecih zdravljenja smo vsem preiskovankam izmerili od endotelija odvisno dilatacijo (EOD), določili koncentracije celičnih adhezijskih molekul (CAM) - ICAM-1, VCAM-1 in E-selectina. Pred zdravljenjem, po 6 in 12 mesecih zdravljenja z raloksifenom smo določili koncentracije kostne alkalne fosfataze (KAF), osteokalcina (OC), C-telopeptida koagena tip I (CTX) in krvnih maščob. Z dvoenergijsko rentgensko absorpciometrijo (DXA) smo, pred in po 12 mesecih zdravljenja, izmerili mineralno kostno gostoto (MKG) ledvene hrbtenice in levega kolka. Rezultati: Po zdravljenju z raloksifenom smo pri preiskovankah z XX v primerjavi z xx genotipom v Xbal polimorfizmu ugotovili signifikantno večjo EOD (P=0,03), v primerjavi z xx genotipom pa je bila le ta mejno večja (P=0,053). Pri nosilkah ne-CC genotipa smo po 6 in 12 mesecih zdravljenja ugotovili pomembno manjše koncentracije celokupnega holesterola (p=0,015 in p=O,O37) in LDL holesterola (p=0,008 in p=0,042), zmanjšanje celokupnega holesterola po 6 mesecih zdravljenja pa je bilo pomembno večje kot pri CC genotipu (P=0,045). Na druge opazovane parametre polimorfizmi v ESRl genu med zdravljenjem z raloksifenom niso vplivali. Prav tako nismo ugotovili pomembnega vpliva preučevanih polimorfizmov na opazovane parametre pred začetkom zdravljenja. (Izvl. skrajšan na 2000 zn.)
Descriptors		OSTEOPOROSIS, POSTMENOPAUSAL CARDIOVASCULAR DISEASES CHOLESTEROL