Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: A multicenter study of 664 patients and 1992 healthy controls

Pietro Invernizzi, Carlo Selmi, Francesca Poli, Sara Frison, Annarosa Floreani, Domenico Alvaro, Piero Almasio, Floriano Rosina, Marco Marzioni, Luca Fabris, Luigi Muratori, Lihong Qi, Michael F. Seldin, M. Eric Gershwin, Mauro Podda, Marco Andreoletti, Angelo Andriulli, Vittorio Baldini, Pier Maria Battezzati, Antonio BenedettiFrancesca Bernuzzi, Francesco B. Bianchi, Ilaria Bianchi, Monica Bignotto, Maria Consiglia Bragazzi, Maurizia Brunetto, Marina Caimi, Lisa Caliari, Nicola Caporaso, Giovanni Casella, Antonietta Casiraghi, Agostino Colli, Massimo Colombo, Dario Conte, Lory Croce, Andrea Crosignani, Lorenzo Dottorini, Carlo Ferrari, Mirella Fraquelli, Cesare E. Frati, Andrea Galli, Ana Lleo, Maria Grazia Mancino, Giovanna Mandelli, Fabio Marra, Renzo Montanari, Valentina Monti, Lorenzo Morini, Filomena Morisco, Grazia Niro, Giuseppe Palasciano, Vincenzo O. Calmieri, Simone Pasini, Antonio Picciotto, Piero Portincasa, Vanila Pozzoli, Giancarlo Spinzi, Mario Strazzabosco, Claudio Tiribelli, Pierluigi Toniutto, Paola Zerminai, Massimo Zuin

Research output: Contribution to journalArticlepeer-review


Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multicenter case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and sex, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR), 3.3; 95% confidence interval (CI), 2.4-4.5] and DRB1*02 (OR 0.9; 95% CI 0.8-1.2) were significantly associated with PBC, whereas alleles DRB1*11 (OR 0.4; 95% CI 0.3-0.4) and DRB1*13 (OR 0.7; 95% CI 0.6-0.9) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. Associated DRB1 alleles were found only in a minority of patients, whereas an additive genetic model is supported by the gene dosage effect for DRB1*11 allele and the interaction of DRB1*11,*13, and *08. Lastly, no significant associations were detected between speci fic DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. In conclusion, we confirm the role for HLA to determine PBC susceptibility and suggest that the effect of HLA is limited to patient subgroups. We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease.

Original languageEnglish
Pages (from-to)1906-1912
Number of pages7
Issue number6
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)


Dive into the research topics of 'Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: A multicenter study of 664 patients and 1992 healthy controls'. Together they form a unique fingerprint.

Cite this