It remains speculative whether the female preponderance (gender ratio up to 10:1) reflects an X-chromosomelinked locus of susceptibility. Alternatively, a protective role of Y-linked genes could be assumed, or just a gender-specific exposure to environmental triggers like cosmetics [116] or nail polishers [117] , as discussed below. However, speculation on a pathomechanistic role for X chromosomal genes was supported by the observation of an increased frequency of X chromosome monosomy in PBC as well as in other autoimmune diseases. This increase in X chromosome monosomy might lead to haploinsufficiency for specific X-linked genes and thereby increase disease predisposition [118] . Case reports of PBC in patients with Turner syndrome (45, X0) also supported this hypothesis [119] .