title: Maternal susceptibility locus for obstetric cholestasis maps to chromosome region 2p13 in Finnish patients.
abstract: BACKGROUND
  Obstetric cholestasis, attributed to maternal hypersensitivity to estrogens, is a pregnancy-specific disorder characterized by pruritus and biochemical cholestasis in the second or third trimester of pregnancy. The pathophysiology of the disorder is incompletely understood, but the familial nature of the disease has long been recognized. Carriership of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency has been reported to be associated with an increased risk of obstetric cholestasis and the gene is located in the p23 region of chromosome 2.
  
  
  METHODS
  On the basis of this information, we conducted population-based linkage disequilibrium (LD) screening to find potential cholestasis-associated loci on chromosome 2. The study was carried out in 47 unrelated control women and in 45 cholestatic women, eight of whom had a positive family history.
  
  
  RESULTS
  During initial screening with chromosome 2-specific microsatellite markers, the tetranucleotide marker D2S1394 was found to be in LD in the 2p13 region. Screening this region with additional microsatellite markers revealed that the adjacent marker D2S1374 was also significantly associated with obstetric cholestasis, whereas no association was found with the markers located in the vicinity of the hydroxyacyl-CoA dehyrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit (HADHA) gene.
  
  
  CONCLUSIONS
  Collectively, these data suggest that there may be a novel obstetric cholestasis-associated gene located in the vicinity of the 2p13 LD region.
authors.affiliation: Dept. of Obstetrics and Gynecology, Kuopio University Hospital, Finland. seppo.heinonen@kuh.fi
authors.forename: S
authors.initials: S
authors.lastname: Heinonen
authors.forename: M L
authors.initials: ML
authors.lastname: Eloranta
authors.forename: J
authors.initials: J
authors.lastname: Heiskanen
authors.forename: K
authors.initials: K
authors.lastname: Punnonen
authors.forename: S
authors.initials: S
authors.lastname: Helisalmi
authors.forename: A
authors.initials: A
authors.lastname: Mannermaa
authors.forename: M
authors.initials: M
authors.lastname: Hiltunen
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D002779:Cholestasis / Q000453:epidemiology / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004967:Estrogens / Q000009:adverse effects; D005260:Female; D005387:Finland / Q000453:epidemiology; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D006967:Hypersensitivity / Q000150:complications; D015810:Linkage Disequilibrium / Q000235:genetics; D019901:Locus Control Region / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*; D011159:Population Surveillance; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000209:etiology*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third
chemical_list: D004967:Estrogens; D005819:Genetic Markers; D015094:3-Hydroxyacyl CoA Dehydrogenases