Maternal susceptibility locus for obstetric cholestasis maps to chromosomeregion 2p13 in Finnish patients

Background: Obstetric cholestasis, attributed to maternal hypersensitivity to estrogens, is a pregnancy-specific disorder characterized by pruritus an d biochemical cholestasis in the second or third trimester of pregnancy. Th e pathophysiology of the disorder is incompletely understood, but the famil ial nature of the disease has long been recognized. Carriership of long-cha in 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency has been repor ted to be associated with an increased risk of obstetric cholestasis and th e 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 cholest atic women, eight of whom had a positive family history. Results: During in itial screening with chromosome 2-specific microsatellite markers, the tetr anucleotide marker D2S1394 was found to be in LD in the 2p13 region. Screen ing this region with additional microsatellite markers revealed that the ad jacent marker D2S1374 was also significantly associated with obstetric chol estasis, whereas no association was found with the markers located in the v icinity of the hydroxyacyl-CoA dehyrogenase/3-ketoacyl-CoA thiolase/enoyl-C oA hydratase, alpha subunit (HADHA) gene. Conclusions: Collectively, these data suggest that there may be a novel obstetric cholestasis-associated gen e located in the vicinity of the 2p13 LD region.