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.
|Titolo:||Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis|
|Autori interni:||SIRCHIA, SILVIA MARIA|
MIOZZO, MONICA ROSA (Primo)
INVERNIZZI, PIETRO (Corresponding)
GRATI, FRANCESCA ROMANA
SELMI, CARLO FRANCESCO (Secondo)
PODDA, MAURO (Ultimo)
|Parole Chiave:||female predisposition; prenatal-diagnosis; Turners-syndrome; blood-cells; QF-PCR; gene; women; identification; autoimmunity; pregnancies|
|Settore Scientifico Disciplinare:||Settore MED/03 - Genetica Medica|
Settore MED/09 - Medicina Interna
|Data di pubblicazione:||ago-2007|
|Digital Object Identifier (DOI):||10.1002/hep.21696|
|Appare nelle tipologie:||01 - Articolo su periodico|
- PubMed Central loading...