SLCO1B1 GENE IN THE ASPECT OF PHARMACOGENETICS

Abstract. Polypeptide which transports the organic anions 1B1 (OATP1B1) – this is the conveyor of human hepatocytes, which mediates the absorption of many endogenous and exogenous compounds. Genetic variations of transporter gene of the solutes 1B1 (SLCO1B1), which encodes a protein OATP1B1, may affect to the pharmacokinetics of drugs and lead to interindividual variation in the response of the body to the received pharmaceuticals.In this article we will discuss current knowledge about expression, functioning of the protein OATP1B1 and the impact of gene polymorphisms SLCO1B1 to the efficacy and safety of various drugs Key words: SLCO1B1, OATP1B1, polymorphism, pharmacogenetics.Белки-транспортеры и фармакогенетика. Генетиче-ская изменчивость ферментов, метаболизирующих ле-карственные препараты, уже давно является признанным фактором, связанным с различием ответов организма на лекарственную терапию и наличием у пациентов побочных эффектов. Семейство цитохромов особенно важно в этом отношении. Другая область, где генотип может значительно влиять на фармакотерапию – это транспортеры. Транспор-теры – это белки, которые переносят эндогенные соеди-нения или ксенобиотики через биологические мембраны при помощи активных или пассивных механизмов. Они могут быть классифицированы как поглощающие или вы-водящие, в зависимости от направления транспортировки [16]. Более чем 400 мембранных транспортеров, которые представляют два основных суперсемейства – транс-портеры растворенных веществ (Solute carriers, SLC) и ATP-связывающие белки-транслокаторы (ATP-binding cassette, ABC), были описаны в геноме человека. Многие из этих транспортеров охарактеризованы на молекулярном уровне и располагаются в тканях и клеточных мембранах организма человека [7]. Степень экспрессии генов, коди-рующих транспортные белки, может оказывать влияние на биодоступность и фармакокинетику различных фарм-препаратов. Кроме того, генетические вариации, такие как однонуклеотидные полиморфизмы (SNPs – single nucleotide polymorphisms) транспортных белков, могут изменять степень поглощения или выведения из клетки лекарственных средств и их метаболитов [16].

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