Frequency of monosomy X in women with primary biliary cirrhosis

• Published in: The Lancet (British edition) Vol. 363; no. 9408; pp. 533 - 535
• Main Authors: Invernizzi, Pietro, Miozzo, Monica, Battezzati, Pier Maria, Bianchi, Ilaria, Grati, Francesca R, Simoni, Giuseppe, Selmi, Carlo, Watnik, Mitchell, Gershwin, M Eric, Podda, Mauro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 14.02.2004; Elsevier Limited
• Subjects: Adult; Age Factors; Aged; Chromosomes; Chromosomes, Human, X - genetics; Chronic Disease; Female; Females; Fluorescence; Genes; Genetic Predisposition to Disease - epidemiology; Hepatitis; Hepatitis C - epidemiology; Humans; Immune Tolerance - genetics; In Situ Hybridization, Fluorescence; Leukocytes; Leukocytes - ultrastructure; Liver; Liver cirrhosis; Liver Cirrhosis, Biliary - epidemiology; Liver Cirrhosis, Biliary - genetics; Middle Aged; Monosomy - diagnosis; Monosomy - genetics; Mutation; Sex Factors; Women
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(04)15541-4

The mechanisms that cause the female predominance of primary biliary cirrhosis (PBC) are uncertain, but the X chromosome includes genes involved in immunological tolerance. We assessed the rate of X monosomy in peripheral white blood cells from 100 women with PBC, 50 with chronic hepatitis C, and 50 healthy controls, by fluorescence in-situ hybridisation. Frequency of X monosomy increased with age in all groups, but was significantly higher in women with PBC than in controls (p<0·0001); age-adjusted back-transformed mean frequencies were 0·050 (95% CI 0·046–0·055) in women with PBC, 0·032 (0·028–0·036) in those with chronic hepatitis C, and 0·028 (0·025–0·032) in controls. We suggest that haploinsufficiency for specific X-linked genes leads to female susceptibility to PBC.