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

Abstract

BackgroundPolymorphisms of vitamin D receptor (VDR) contribute to the pathogenesis of multiple autoimmune conditions.MethodsWe 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.ResultsThe 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.ConclusionIn 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.

The Significance of Vitamin D Receptor Gene Polymorphisms for Susceptibility to Hepatocellular Carcinoma in Subjects Infected with Hepatitis C Virus

“…The pathogenic mechanisms of genetic factors [gene polymorphisms of cytokines, growth factors, and receptors] relating chronic HCV to HCC development are not entirely well established [20]. VDR gene polymorphisms have been described in several chronic liver diseases such as liver cirrhosis [21], autoimmune hepatitis [22], primary sclerosing cholangitis [23] and primary biliary cirrhosis [24]. Moreover, it has been reported that there is a significant association between polymorphisms of VDR gene and the occurrence of HCC in alcoholic liver cirrhosis in Caucasian subjects [25], in HBV-infected patients [26] and even in patients with chronic HCV [27].…”

Patient-reported outcome measures used in patients with primary sclerosing cholangitis: a systematic review

“…Ten disease-specific measures included: the Short form Liver Disease Quality of Life questionnaire (LDQOL 1.0) [ 32 ]; CLDQ [ 27 , 29 , 38 , 39 , 42 , 43 ]; the NIDDK-QA [ 26 , 28 ]; Rome II Modular Questionnaire; the Cleveland Global Quality of Life questionnaire (CGQOL) [ 34 ]; the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) [ 32 , 47 ]; Oresland scale; PSC PRO; [ 43 ] PBC-27 [ 35 , 40 , 41 ]; and PBC-40 [ 32 , 35 , 40 , 41 , 43 ].…”

Primary Sclerosing Cholangitis and Psychological Wellbeing: A Scoping Review

“…From the studies we identified, a raised serum alkaline phosphatase was linked to worsened mental health. 12 The presence of Apa-I polymorphism of vitamin D receptors was found to be associated with poorer quality of life, mental-and emotional-healthrelated scores 60 Finally, the other two existing studies found that neither serum autotaxin nor plasma tyrosine concentrations affected mental health or quality of life. 61,62…”