Keratin variants are overrepresented in primary biliary cirrhosis and associate with disease severity
dc.contributor.author | Zhong, Bihui | en_US |
dc.contributor.author | Strnad, Pavel | en_US |
dc.contributor.author | Selmi, Carlo | en_US |
dc.contributor.author | Invernizzi, Pietro | en_US |
dc.contributor.author | Tao, Guo-Zhong | en_US |
dc.contributor.author | Caleffi, Angela | en_US |
dc.contributor.author | Chen, Minhu | en_US |
dc.contributor.author | Bianchi, Ilaria | en_US |
dc.contributor.author | Podda, Mauro | en_US |
dc.contributor.author | Pietrangelo, Antonello | en_US |
dc.contributor.author | Gershwin, M. Eric | en_US |
dc.contributor.author | Omary, M. Bishr | en_US |
dc.date.accessioned | 2009-08-12T15:34:05Z | |
dc.date.available | 2010-10-05T18:27:29Z | en_US |
dc.date.issued | 2009-08 | en_US |
dc.identifier.citation | Zhong, Bihui; Strnad, Pavel; Selmi, Carlo; Invernizzi, Pietro; Tao, Guo-Zhong; Caleffi, Angela; Chen, Minhu; Bianchi, Ilaria; Podda, Mauro; Pietrangelo, Antonello; Gershwin, M. Eric; Omary, M. Bishr (2009). "Keratin variants are overrepresented in primary biliary cirrhosis and associate with disease severity Potential conflict of interest: Nothing to report. ." Hepatology 50(2): 546-554. <http://hdl.handle.net/2027.42/63532> | en_US |
dc.identifier.issn | 0270-9139 | en_US |
dc.identifier.issn | 1527-3350 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/63532 | |
dc.description.abstract | Keratins (K) 8 and 18 variants predispose carriers to the development of end-stage liver disease and patients with chronic hepatitis C to disease progression. Hepatocytes express K8/K18, whereas biliary epithelia express K8/K18/K19. K8-null mice, which are predisposed to liver injury, spontaneously develop anti-mitochondrial antibodies (AMA) and have altered hepatocyte mitochondrial size and function. There is no known association of K19 with human disease and no known association of K8/K18/K19 with human autoimmune liver disease. We tested the hypothesis that K8/K18/K19 variants associate with primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterized by the presence of serum AMA. In doing so, we analyzed the entire exonic regions of K8/K18/K19 in 201 Italian patients and 200 control blood bank donors. Five disease-associated keratin heterozygous variants were identified in patients versus controls (K8 G62C/R341H/V380I, K18 R411H, and K19 G17S). Four variants were novel and included K19 G17S/V229M/N184N and K18 R411H. Overall, heterozygous disease-associated keratin variants were found in 17 of 201 (8.5%) PBC patients and 4 of 200 (2%) blood bank donors ( P < 0.004, odds ratio = 4.53, 95% confidence interval = 1.5–13.7). Of the K19 variants, K19 G17S was found in three patients but not in controls and all K8 R341H (eight patients and three controls) associated with concurrent presence of the previously described intronic K8 IVS7+10delC deletion. Notably, keratin variants associated with disease severity (12.4% variants in Ludwig stage III/IV versus 4.2% in stages I/II; P < 0.04, odds ratio = 3.25, 95% confidence interval = 1.02–10.40), but not with the presence of AMA. Conclusion: K8/K18/K19 variants are overrepresented in Italian PBC patients and associate with liver disease progression. Therefore, we hypothesize that K8/K18/K19 variants may serve as genetic modifiers in PBC. (H EPATOLOGY 2009.) | en_US |
dc.format.extent | 913349 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Hepatology | en_US |
dc.title | Keratin variants are overrepresented in primary biliary cirrhosis and associate with disease severity | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Molecular & Integrative Physiology, University of Michigan School of Medicine, Ann Arbor, MI ; University of Michigan, School of Medicine, Department of Molecular & Integrative Physiology, 7744 Medical Science II, 1301 E. Catherine Street, Ann Arbor, MI 48109 | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China ; Palo Alto VA Medical Center and Stanford University School of Medicine, Palo Alto, CA ; These authors contributed equally to this work. ; Division of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China | en_US |
dc.contributor.affiliationother | Palo Alto VA Medical Center and Stanford University School of Medicine, Palo Alto, CA ; Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany | en_US |
dc.contributor.affiliationother | Division of Internal Medicine and Hepatobiliary Immunopathology Unit, Rozzano, Italy ; University of Milan, Rozzano, Italy | en_US |
dc.contributor.affiliationother | Division of Internal Medicine and Hepatobiliary Immunopathology Unit, Rozzano, Italy | en_US |
dc.contributor.affiliationother | Palo Alto VA Medical Center and Stanford University School of Medicine, Palo Alto, CA | en_US |
dc.contributor.affiliationother | Center for Hemochromatosis, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China | en_US |
dc.contributor.affiliationother | Division of Internal Medicine and Hepatobiliary Immunopathology Unit, Rozzano, Italy ; University of Milan, Rozzano, Italy | en_US |
dc.contributor.affiliationother | Division of Internal Medicine and Hepatobiliary Immunopathology Unit, Rozzano, Italy ; University of Milan, Rozzano, Italy | en_US |
dc.contributor.affiliationother | Center for Hemochromatosis, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy | en_US |
dc.contributor.affiliationother | Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, Davis, CA | en_US |
dc.identifier.pmid | 19585610 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/63532/1/23041_ftp.pdf | |
dc.identifier.doi | 10.1002/hep.23041 | en_US |
dc.identifier.source | Hepatology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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