title: Common polymorphisms in the CYP7A1 gene do not contribute to variation in rates of bile acid synthesis and plasma LDL cholesterol concentration.
abstract: Transcriptional regulation of the cholesterol 7alpha-hydroxylase (CYP7AI) gene is of critical importance for bile acid and cholesterol metabolism. We evaluated the physiological significance of two common polymorphisms (-203C/A and -469T/C) in the promoter region of the CYP7AI gene. No evidence was found for physiological differences between either the -203C and -203A alleles or the -469T and -469C alleles in transient transfection studies using native 834bp promoter constructs. Moreover, no association was observed between the CYP7AI promoter polymorphisms and the hepatic cholesterol 7alpha-hydroxylase activity and parameters of bile acid synthesis rates, as analyzed in subjects with gallstone disease. In addition, no relationships were found between the promoter polymorphisms and plasma LDL cholesterol concentration in association studies conducted in three different groups of middle-aged Swedish men. Finally, near complete allelic association was found between the two promoter polymorphisms and the IVS6+363G/A polymorphism at the 3' end of the CYP7AI gene (|D'|=0.98), indicating strong linkage disequilibrium across the whole CYP7AI gene. It is concluded that common polymorphisms of the CYP7A1 gene do not contribute to variation in cholesterol 7alpha-hydroxylase activity, rates of bile acid synthesis and plasma LDL cholesterol concentration in humans.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institute at Huddinge University Hospital, SE-14186 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Abrahamsson
authors.forename: Sergey
authors.initials: S
authors.lastname: Krapivner
authors.forename: Ulf
authors.initials: U
authors.lastname: Gustafsson
authors.forename: Olle
authors.initials: O
authors.lastname: Muhrbeck
authors.forename: Gösta
authors.initials: G
authors.lastname: Eggertsen
authors.forename: Inger
authors.initials: I
authors.lastname: Johansson
authors.forename: Irene
authors.initials: I
authors.lastname: Persson
authors.forename: Bo
authors.initials: B
authors.lastname: Angelin
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
authors.forename: Curt
authors.initials: C
authors.lastname: Einarsson
authors.forename: Ferdinand M
authors.initials: FM
authors.lastname: van't Hooft
mesh_terms: D001647:Bile Acids and Salts / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002783:Cholestenones / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood*; D005820:Genetic Testing; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D001647:Bile Acids and Salts; D002783:Cholestenones; D008078:Cholesterol, LDL; C002656:7 alpha-hydroxy-4-cholesten-3-one; D002790:Cholesterol 7-alpha-Hydroxylase