title: Association of single nucleotide polymorphisms of the bile salt export pump gene with intrahepatic cholestasis of pregnancy.
abstract: BACKGROUND
  We determined whether genetic variability in the gene encoding the bile salt export pump (BSEP) contributes to individual differences in susceptibility to the development of intrahepatic cholestasis of pregnancy (ICP).
  
  
  METHODS
  The study involved 57 affected and 115 healthy control pregnant women who were genotyped for two single nucleotide polymorphisms (SNPs) in the BSEP gene. Chi-square analysis was used to assess genotype and allele frequency differences between the cholestatic and control groups. In addition, single locus analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, among the cholestatic and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization (EM) algorithm.
  
  
  RESULTS
  The genotype and allele frequency distribution of the two intragenic SNPs in the ICP and control groups revealed significant evidence of association with the exon 28 SNP (P=0.04 and P=0.02, respectively). In addition, a borderline allele association was noted with the intron 19 SNP (P=0.08). Although the overall distribution of estimated haplotypes of intron 19 and exon 28 SNPs did not differ between the ICP and control groups, the most common haplotype, A-G, was significantly overrepresented in the ICP group (P=0.02), at an odds ratio of 1.73 (95% CI: 1.08-2.74).
  
  
  CONCLUSIONS
  The use of two intragenic SNPs in both single locus and haplotype analyses of association suggests that the BSEP gene is a susceptibility gene in intrahepatic cholestasis of pregnancy.
authors.affiliation: Dept. of Obstetrics and Gynecology, Kuopio University and University Hospital, Kuopio, Finland.
authors.forename: M L
authors.initials: ML
authors.lastname: Eloranta
authors.forename: T
authors.initials: T
authors.lastname: Häkli
authors.forename: M
authors.initials: M
authors.lastname: Hiltunen
authors.forename: S
authors.initials: S
authors.lastname: Helisalmi
authors.forename: K
authors.initials: K
authors.lastname: Punnonen
authors.forename: S
authors.initials: S
authors.lastname: Heinonen
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D002780:Cholestasis, Intrahepatic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications; D012189:Retrospective Studies
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters