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  • In clinical part of the study the hypothesis that hypercholesterolemic patients - carriers of -203C variant in cholesterol 7alpha-hydroxylase (CYP7A1) gene respond to 4-week therapy with bile acid sequestrant by more pronounced decrease in cholesterolemia than -203A variant carriers will be tested. The dynamics of changes in concentration of cholesterol, lipoproteins, glucose and factors affecting insulin sensitivity induced by changes in bile acid metabolism after sequestrant administration will be studied in healthy volunteers. It will be also analyzed how the changes in bile acid metabolism affect glucoregulation and thyroid function. In molecular biology part of the project the dual luciferase assay will be used to analyze in detail the role of particular polymorphisms in promoter region and first intron of CYP7A1 gene (polymorphisms being in tight linkage disequilibrium with -203A/C polymorphism) in regulation of cholesterol-7alpha-hydroxylase gene expression. (en)
  • V klinické části projektu bude testována hypotéza, že hypercholesterolemičtí pacienti - nositelé varianty -203C v genu kódujícím cholesterol-7alfa-hydroxylasu (CYP7A1) odpovídají na 4týdenní léčbu sekvestranty žlučových kyselin podstatně větším poklesem cholesterolémie než nositelé varianty -203A. Dynamika změn koncentrace cholesterolu, lipoproteinů, glukózy a faktorů ovlivňujících inzulínosenzitivitu indukovaných změnami v metabolismu žlučových kyselin po podání sekvestrantu bude studována u zdravých dobrovolníků. Dále bude analyzováno, jak změny v metabolismu žlučových kyselin ovlivní glykoregulaci a funkci štítné žlázy. V molekulárně biologické části projektu bude metodou duálního luciferasového stanovení detailně analyzována úloha polymorfismů v promotorové oblasti a 1. intronu genu kódujícího CYP7A1 v regulaci exprese cholesterol-7alfa-hydroxylasy. (cs)
Title
  • Polymorfismus cholesterol-7alfa-hydroxylasy jako prediktor odpovídavosti cholesterolémie (cs)
  • Cholesterol 7alpha-hydroxylase polymorphism as a predictor cholesterolemia responsiveness (en)
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  • cholesterol 7alpha-hydroxylase; genetics; cholesterol; bile acids; bile acid sequestrants; insulin sensitivity (en)
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