HUMAN LEUKOCYTE ANTIGEN POLYMORPHISMS IN ITALIAN PRIMARY BILIARY CIRRHOSIS: A MULTICENTER STUDY OF 664 PATIENTS AND 1992 HEALTHY CONTROLS
Autor: | Invernizzi, P, Selmi, C, Poli, F, Frison, S, Floreani, A, Alvaro, D, Almasio, P, Rosina, F, Marzioni, M, Fabris, L, Muratori, L, Qi, L, Seldin, Mf, Gershwin, Me, Podda, M, Andreoletti, M, Andriulli, A, Baldini, V, Battezzati, Pm, Benedetti, A, Bernuzzi, F, Bianchi, Fb, Bianchi, I, Bignotto, M, Bragazzi, Mc, Brunetto, M, Caimi, M, Caliari, L, Caporaso, N, Casella, G, Casiraghi, A, Colli, A, Colombo, M, Conte, D, Croce, L, Crosignani, A, Dottorini, L, Ferrari, C, Fraquelli, M, Frati, Ce, Galli, A, Lleo, A, Mancino, Mg, Mandelli, G, Marra, F, Montanari, R, Monti, V, Morini, L, Morisco, F, Niro, G, Palasciano, G, Calmieri, Vo, Pasini, S, Picciotto, A, Portincasa, P, Pozzoli, V, Spinzi, G, Strazzabosco, M, Tiribelli, C, Toniutto, Pierluigi, Zerminai, P, Zuin, M. |
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Přispěvatelé: | Invernizzi, P, Selmi, C, Poli, F, Frison, S, Floreani, A, Alvaro, D, Almasio, P, Rosina, F, Marzioni, M, Fabris, L, Muratori, L, Qi, L, Seldin, M, Gershwin, M, Podda, M, Andreoletti, M, Andriulli, A, Baldini, V, Battezzati, P, Benedetti, A, Bernuzzi, F, Bianchi, F, Bianchi, I, Bignotto, M, Bragazzi, M, Brunetto, M, Caimi, M, Caliari, L, Caporaso, N, Casella, G, Casiraghi, A, Colli, A, Colombo, M, Conte, D, Croce, L, Crosignani, A, Dottorini, L, Ferrari, C, Fraquelli, M, Frati, C, Galli, A, Lleo, A, Mancino, M, Mandelli, G, Marra, F, Montanari, R, Monti, V, Morini, L, Morisco, F, Niro, G, Palasciano, G, Calmieri, V, Pasini, S, Picciotto, A, Portincasa, P, Pozzoli, V, Spinzi, G, Strazzabosco, M, Tiribelli, C, Toniutto, P, Zerminai, P, Zuin, M, Invernizzi P, Selmi C, Poli F, Frison S, Floreani A, Alvaro D, Almasio P, Rosina F, Marzioni M, Fabris L, Muratori L, Qi L, Seldin MF, Gershwin ME, Podda M, Andreoletti M, Andriulli A, Baldini V, Battezzati PM, Benedetti A, Bernuzzi F, Bianchi FB, Bianchi I, Bignotto M, Bragazzi MC, Brunetto M, Caimi M, Caliari L, Caporaso N, Casella G, Casiraghi A, Colli A, Colombo M, Conte D, Croce L, Crosignani A, Dottorini L, Ferrari C, Fraquelli M, Frati CE, Galli A, Lleo A, Mancino MG, Mandelli G, Marra F, Montanari R, Monti V, Morini L, Morisco F, Niro G, Palasciano G, Calmieri VO, Pasini S, Picciotto A, Portincasa P, Pozzoli V, Spinzi G, Strazzabosco M, Tiribelli C, Toniutto P, Zerminai P, Zuin M., Invernizzi P, Selmi C, Poli F, Frison S, Floreani A, Alvaro D, Almasio P, Rosina F, Marzioni M, Fabris L, Muratori L, Qi L, Seldin MF, Gershwin ME, Podda M, Italian PBC Genetic Study Group, Seldin, Mf, Gershwin, Me, Croce', Saveria |
Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: |
Proband
Liver Cirrhosis Male Cohort Studies Primary biliary cirrhosis Gene Frequency Models Genotype 80 and over Medicine skin and connective tissue diseases Aged 80 and over Settore MED/12 - Gastroenterologia Liver Cirrhosis Biliary Medicine (all) Biliary Middle Aged Italy HLA-DRB1 Chain Female Case-Control Studie Human musculoskeletal diseases Adult Human leukocyte antigen Article Genetic Genetic model Humans Genetic Predisposition to Disease Polymorphism Allele frequency Aged Polymorphism Genetic Hepatology Models Genetic business.industry Case-control study Odds ratio HLA-DR Antigens medicine.disease HLA-DR Antigen Case-Control Studies Immunology primary bilairy cirrhosis genetics Cohort Studie business HLA-DRB1 Chains |
Popis: | 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. Copyright © 2008 by the American Association for the Study of Liver Diseases. |
Databáze: | OpenAIRE |
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