Exploring the genetic role of the HLA-DPB1 locus in Chileans with intrahepatic cholestasis of pregnancy

• Published in: Journal of hepatology Vol. 24; no. 3; pp. 320 - 323
• Main Authors: Mella, Juan G., Roschmann, Elke, Glasinovic, Juan C., Alvarado, Alejandra, Scrivanti, Mirella, Volk, Brigitte A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.03.1996; Elsevier
• Subjects: Alleles; Base Sequence; Biological and medical sciences; Chile - epidemiology; Cholestasis, Intrahepatic - epidemiology; Cholestasis, Intrahepatic - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Genes, MHC Class II - genetics; Genetic susceptibility; Genotype; HLA-DP Antigens - genetics; HLA-DP beta-Chains; HLA-DPB1; Humans; Intrahepatic cholestasis of pregnancy; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Molecular Sequence Data; Oligonucleotide Probes - chemistry; Other diseases. Semiology; Polymerase Chain Reaction; Polymorphism, Genetic; Pregnancy; Pregnancy Complications; Prevalence; Recurrence; South America; Chile; America; Genetic susceptibility; HLA-DPB1; Intrahepatic cholestasis of pregnancy; Human; HLA-System; Pregnancy disorders; Hepatic disease; Biliary tract disease; Endemy; Pregnancy; Intrahepatic cholostasis; Gene; Risk factor; Predisposition; Digestive diseases; Complication; Woman; Localization
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(96)80011-0

Background/Aims: Intrahepatic cholestasis of pregnancy is a rare disease of unknown etiology, with a strikingly higher prevalence in Chile than in most other countries. Although several studies suggest that a genetic predisposition is involved in the pathogenesis, no genetic disease-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 30 unrelated multiparous women without a personal or family history of this disease among a Chilean population. The polymorphic second exon of 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. Results: Out of more than 50 HLA-DPB1 alleles presently known, 13 were represented in the analyzed groups. Patients with ICP had a higher frequency of the allele DPB1 *0402 when compared to controls (69% vs 43%). This difference failed to reach statistical significance (χ 2=2.81, corrected p > 0.5). No significant differences were observed between the frequencies of other detected HLA-DPB1 alleles in the analyzed groups. Conclusion: In this study, we observed a high frequency of the allele HLA-DPB1 *0402 among Chilean patients with recurrent ICP, but no association of the disease with HLA-DPB1 alleles. Therefore, HLA-DPB1 alleles do not play a major role in determining susceptibility or resistance to intrahepatic cholestasis of pregnancy.