title: Genetic variations in bile acid homeostasis are not overrepresented in alcoholic cirrhosis compared to patients with heavy alcohol abuse and absent liver disease.
abstract: Increased serum bile salt levels have been associated to a single-nucleotide polymorphism in the bile salt export pump (BSEP; ABCB11) in several acquired cholestatic liver diseases but there is little evidence in alcoholic liver disease (ALD). Furthermore, a crosstalk between vitamin D and bile acid synthesis has recently been discovered. Whether this crosstalk has an influence on the course of ALD is unclear to date. Our aim was to analyse the role of genetic polymorphisms in BSEP and the vitamin D receptor gene (NR1I1) on the emergence of cirrhosis in patients with ALD. Therefore, 511 alcoholic patients (131 with cirrhosis and 380 without cirrhosis) underwent ABCB11 genotyping (rs2287622). Of these, 321 (131 with cirrhosis and 190 without cirrhosis) were also tested for NR1I1 polymorphisms (bat-haplotype: BsmI rs1544410, ApaI rs7975232 and TaqI rs731236). Frequencies of ABCB11 and NR1I1 genotypes and haplotypes were compared between alcoholic patients with and without cirrhosis and correlated to serum bile salt, bilirubin and aspartate aminotransferase levels in those with cirrhosis. Frequencies of ABCB11 and NR1I1 genotypes and haplotypes did not differ between the two subgroups and no significant association between genotypes/haplotypes and liver function tests could be determined for neither polymorphism. We conclude that ABCB11 and NR1I1 polymorphisms are obviously not associated with development of cirrhosis in patients with ALD.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich (USZ), CH-8091 Zurich, Switzerland.
authors.forename: Natalie
authors.initials: N
authors.lastname: Many
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Johannes
authors.initials: J
authors.lastname: Schmitt
authors.forename: Bruno
authors.initials: B
authors.lastname: Stieger
authors.forename: Michael
authors.initials: M
authors.lastname: Soyka
authors.forename: Pascal
authors.initials: P
authors.lastname: Frei
authors.forename: Oliver
authors.initials: O
authors.lastname: Götze
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D000437:Alcoholism; D000483:Alleles; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D018167:Receptors, Calcitriol