Author/Editor		Marc, Janja
Title		Receptor vitamina D: zgradba, delovanje in genetika
Translated title		Vitamin D receptor: structure, function and genetics
Type		članek
Source		Farm Vestn
Vol. and No.		Letnik 49, št. 4
Publication year		1998
Volume		str. 459-67
Language		slo
Abstract		The biological effects of vitamin D are mediated by specific intracellular receptor, vitamin D receptor. The vitamin D receptor is a protein with 427 amino acid residues. It is a member of the nuclear receptor family in which proteins include two functional domains: for DNA binding and for ligand binding domain. The structure alows them to cooperative at the signal transduction and the transcriptional regulation in target cells. The vitamin D receptor is a transcriptional factor which stimulates the synthesis of calcium binding proteins: osteocalcin and osteopontin in the bone and calbindin 9K and 28K in the small intestine as well as two enzymes: alkaline phosphatase and 24 hydroxylase. The vitamin D receptor gene is located on 12q chromosome and includes nine exons. Mostly the VDR gene analysis have been performed in order to diagnose the hereditary rickets and osteoporosis. There are 15 point mutations of the vitamin D receptor gene caused the hereditary vitamin D resistant rickets. On the contrary the the relationship between Bsm1-, Apa1-, Taq1- and Fok1-vitamin D receptor gene polymorphisms and osteoporosis is inconsistent. It seems in the osteoporosis there are many different genes included.
Summary		Vitamin D lahko deluje šele po vezavi na specifični intracelularni receptor, vitamin D receptor. Ta je mediator tako kalciotropnih, kot tudi imunomodulatornih, antiproliferativnih in drugih učinkov tega vitamina, ki ga pravzaprav zaradi načina delovanja uvrščamo med hormone. Receptor vitamin D je protein s 427 aminokislinskimi ostanki. Spada v družino jedrnih receptorjev, katerih zgradba vključuje področje za vezavo DNA in področje za vezavo liganda. Takšna zgradba mu omogoča prenos (transdukcijo) signalne molekule (hormona) do jedra ter nadzor nad izražanjem (ekspresijo)nekaterih genov v ciljni celici. Pri tem deluje kot transkripcijski faktor. Na ta način vzpodbuja sintezo proteinov, ki vežejo in prenašajo kalcijeve ione. V kosteh sta to ostekalcin in osteopontin, v tankem črevesju pa kaldbindin 9K in kalbindin 28K. Prav tako je odgovoren tudi za sintezo dveh encimov in sicer alkalne fosfataze ter 24-hidroksilaze. Gen za recptor vitamina D se nahaja na dolgi ročici kromosoma 12. Obsega 75 kilobaz dolgo zaporedje baz in vključuje devet eksonov. Največ analiz gena za VDR so opravili, da bi odkrili rahitis in osteoporozo. Odkritih je bilo 15 točkastih mutacij, ki se klinično izkazujejo kot rahitis. Nasprotno pa povezanost Bsm1-, Apa1-, Taq1-, in Fok1-polimorfizmov tega gena z osteoporozo ni dokončno potrjena. Zdi se, da je za razvoj osteoporoze odgovornih več genov, ki jih vseh še ne poznamo.
Descriptors		VITAMIN D VITAMIN D-BINDING PROTEIN RECEPTORS, CALCITRIOL RICKETS OSTEOPOROSIS POLYMORPHISM (GENETICS) MUTATION