ApaI polymorphism of vitamin D receptor affects health-related quality of life in patients with primary sclerosing cholangitis

BACKGROUND: Polymorphisms of vitamin D receptor (VDR) contribute to the pathogenesis of multiple autoimmune conditions. METHODS: We investigated the incidence of VDR polymorphisms (rs1544410-BsmI; rs7975232-ApaI; rs731236-TaqI) in a group of patients with primary sclerosing cholangitis (PSC, n = 275) and in healthy controls (n = 376). Additionally, correlations of the VDR polymorphisms with clinical and biochemical factors of the disease were analysed. RESULTS: The genotype and allele distributions of these polymorphisms in PSC patients were similar to those observed in controls. However, the ApaI polymorphism was associated with an impaired health-related quality of life (HRQoL). The generic SF-36 questionnaire showed that the Role-Physical (p = 0.01), Role-Emotional (p = 0.01), Physical Component Summary (p = 0.01) and Mental Component Summary (p = 0.003) scores were significantly affected. Similarly, the disease-specific questionnaires, PBC-40 and PBC-27, demonstrated that carriers of the C allele suffered from more severe Itch (p = 0.03 assessed by PBC-40 and PBC-27), more Fatigue (p = 0.02 assessed by PBC-40 and PBC-27) and Impaired Cognitive Capacity (p = 0.04 and p = 0.03). Correspondingly, individuals who were AA homozygotes (non-carriers of the C allele of ApaI) had higher summary scores for the Physical (p = 0.01) and Mental Components (p = 0.006) measured with SF-36. Moreover, they experienced less itch (p = 0.03) and less Fatigue (p = 0.03) and had better Cognitive Abilities (p = 0.04) as assessed by the PBC-40 and PBC-27 questionnaires. No associations between other VDR polymorphisms and clinical or laboratory findings were made. CONCLUSION: In summary, this study is the first to show that the ApaI polymorphisms in VDR may exert an effect on disease-related symptoms and quality of life in patients with PSC.