Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis

Authors

  • Monica Miozzo,

    1. Medical Genetics Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
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    • These authors contributed equally to this work.

  • Carlo Selmi,

    1. Division of Internal Medicine and Liver Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
    2. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA
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    • These authors contributed equally to this work.

  • Barbara Gentilin,

    1. Medical Genetics Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
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  • Francesca R. Grati,

    1. Medical Genetics Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
    2. Cytogenetics and Molecular Biology Unit, TOMA Laboratories, Busto Arsizio, Varese, Italy
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  • Silvia Sirchia,

    1. Medical Genetics Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
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  • Sabine Oertelt,

    1. Division of Internal Medicine and Liver Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
    2. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA
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  • Massimo Zuin,

    1. Division of Internal Medicine and Liver Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
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  • M. Eric Gershwin,

    1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA
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  • Mauro Podda,

    1. Division of Internal Medicine and Liver Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
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  • Pietro Invernizzi

    Corresponding author
    1. Division of Internal Medicine and Liver Unit, San Paolo Hospital School of Medicine, University of Milan, Milan, Italy
    • Division of Internal Medicine and Liver Unit, San Paolo Hospital School of Medicine, University of Milan, via di Rundiní 8, 20142, Milan, Italy
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    • fax: (39) 0250323089


  • Potential conflict of interest: Nothing to report

Abstract

Recent work has demonstrated enhanced X monosomy in women with primary biliary cirrhosis (PBC) as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. To further our understanding of these events, we have investigated the mechanisms of X chromosome loss and X chromosome inactivation (XCI) in 166 women with PBC and 226 rigorously age-matched healthy and liver disease controls. X chromosome analysis and determination of loss pattern was performed by quantitative fluorescent polymerase chain reaction (QF-PCR) with 4 X-linked short tandem repeats. Further definition of the XCI was based on analysis of methylation-sensitive restriction sites. Importantly, in PBC the X chromosome loss occurs not only more frequently but also in a preferential fashion. This observation supports our thesis that the enhanced X monosomy involves only one parentally derived chromosome and is not secondary to a constitutive non random pattern of XCI. In fact, in the presence of monosomy, the lost X chromosome is necessarily the inactive homologue. Conclusion: The finding that the X chromosome loss is preferential suggests the critical involvement of X chromosome gene products in the female predisposition to PBC and also emphasizes the need to determine the parental origin of the maintained chromosome to investigate the role of imprinting. (HEPATOLOGY 2007.)

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