Jg. Mella et al., EXPLORING THE GENETIC ROLE OF THE HLA-DPB1 LOCUS IN CHILEANS WITH INTRAHEPATIC CHOLESTASIS OF PREGNANCY, Journal of hepatology, 24(3), 1996, pp. 320-323
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.