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

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

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96 Citations (Scopus)


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 specific 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
Publication statusPublished - 2008

All Science Journal Classification (ASJC) codes

  • Hepatology


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