EXPLORING THE GENETIC ROLE OF THE HLA-DPB1 LOCUS IN CHILEANS WITH INTRAHEPATIC CHOLESTASIS OF PREGNANCY

Background/Aims: Intrahepatic cholestasis of pregnancy is a rare disea se of unknown etiology, with a strikingly higher prevalence in Chile t han in most other countries, Although several studies suggest that a g enetic predisposition is involved in the pathogenesis, no genetic dise ase-marker has so far been identified, Using a recently developed HLA- genotyping technique, we performed an association study with a highly polymorphic HLA class II gene in patients with recurrent intrahepatic cholestasis of pregnancy and normal control patients. Methods: Genomic DNA was extracted from 26 unrelated patients with recurrent ICP and 3 0 unrelated multiparous women without a personal or family history of this disease among a Chilean population, The polymorphic second exon o f the HLA-DPB1 gene was amplified by the polymerase chain reaction and hybridized with 25 sequence-specific oligonucleotide probes to assign the HLA-DPB1 alleles on the basis of known sequence variations. Resul ts: Out of more than 50 HLA-DPB1 alleles presently known, 13 were repr esented in the analyzed groups. Patients with ICP had a higher frequen cy of the allele DPB10402 when compared to controls (69% vs 43%). Thi s difference failed to reach statistical significance (chi(2)=2.81, co rrected p>0.5). No significant differences were observed between the f requencies of other detected HLA-DPB1 alleles in the analyzed groups. Conclusion: In this study, we observed a high frequency of the allele HLA-DPB10402 among Chilean patients with recurrent ICP, but no associ ation of the disease with HLA-DPB1 alleles, Therefore, HLA-DPB1 allele s do not play a major role in determining susceptibility or resistance to intrahepatic cholestasis of pregnancy.