Vitamin-D Receptor-Gene Polymorphisms Affect Quality of Life in Patients with Autoimmune Liver Diseases

Abstract

Vitamin D deficiency has been associated with depressive symptoms and reduced physical functioning. The aim of the study was to characterize the relationship between polymorphisms of the vitamin D receptor (VDR) gene and the quality of life in patients with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Three polymorphisms of the VDR gene (TaqI-rs731236, BsmI-rs1544410, and ApaI-rs7975232) were analyzed in patients with AIH (n = 142) and PBC (n = 230) and in healthy individuals (n = 376). Patient quality of life was assessed by validated questionnaires such as Medical Outcomes Study Short-Form 36 (SF-36), State Trait Anxiety Inventory (STAI), Modified Fatigue-Impact Scale (MFIS), Patient-Health Questionnaire 9 (PHQ-9), and PBC-40. The TaqI C and ApaI A alleles are risk alleles in both AIH and PBC, and a significant dominance of the A allele in BsmI was observed in AIH patients. In terms of quality of life, the presence of the CC or CT TaqI genotype was associated with emotional reactions, including the fatigue and the cognitive skills of patients with PBC, whereas in the group of AIH patients, homozygotes CC of TaqI, AA of BsmI, and AA of ApaI had worse physical, social, emotional, and mental function. The genetic variations of VDR gene can influence individual susceptibility to develop chronic autoimmune liver diseases such as AIH and PBC and affect quality of life.

MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis

“…Analyses of PBC and PSC risk loci in patients with AIH without cholestatic variants revealed that part of the genetic susceptibility for AIH coincides with PBC and PSC 12 . Other non-HLA susceptibility polymorphisms, for example, tumor necrosis factor alfa (TNF-alpha) 19 or vitamin D receptor (VDR) 20 , 21 , were also associated with AIH in the previous studies. A recently published single-center analysis of 239 adult patients with AIH demonstrated that carriers of the minor PNPLA3 p.I148M allele are characterized by advanced liver fibrosis according to the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4) 22 .…”

Pathogenesis of autoimmune hepatitis

“…The genetic susceptibility and severity of disease in British and Brazilian type II AIH patients are related to HLA-DRB1*0301 alleles[ 1 - 3 ]. Gene mutations other than HLA are also related to AIH susceptibility or progression: Fas-670a/g and Fas-1377g/a polymorphisms[ 5 ], VDR[ 6 ], and GATA-2[ 7 ] are closely related to the onset of AIH. The high-affinity combination of y1 and -1993 c alleles inhibits expression of tbx21, which may inhibit the occurrence of AIH I by inhibiting the type 1 immune response[ 8 ].…”

“…Vitamin D deficiency usually exists in patients with immune-mediated liver disease and non-liver disease, and is related to the histological severity of AIH, advanced liver fibrosis, the ineffectiveness of conventional glucocorticoid therapy, and the need for liver transplantation[ 19 ]. Another study found that genetic variants of VDR genes (TaqI-rs731236, BsmI-rs1544410 and ApaI-rs7975232) can affect the susceptibility of individuals to chronic autoimmune liver diseases (such as AIH and primary biliary cholangitis, and affect quality of life[ 6 ].…”

Risk of fractures and postfracture mortality in 3980 people with primary biliary cholangitis: A population‐based cohort study

“…The incidence of osteoporosis is three-to fourfold higher in people with PBC [5,6]. The majority of people with PBC (80%-90%) are female [7]. The impaired absorption of fat-soluble vitamins in PBC appears to be a major factor in the development of bone disease.…”