Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations

J Hepatol. 2009 Jun;50(6):1202-9. doi: 10.1016/j.jhep.2009.01.015. Epub 2009 Mar 5.


Background/aims: Vitamin D receptor (VDR) agonists have recently been identified as potent immunomodulators capable of inhibiting Th1-mediated immune response, leading us to consider the hypothesis that functional VDR polymorphisms might contribute to enhanced risk for developing primary biliary cirrhosis (PBC), a Th1-mediated autoimmune disease. In the current study, we aimed at elucidating the genetic association of VDR polymorphisms with susceptibility to PBC in Japanese and Italian populations.

Methods: We enrolled 334 PBC patients (195 Japanese and 139 Italians), as well as 334 age- and sex-matched controls (179 Japanese and 156 Italians). VDR genotyping was performed by PCR-RFLP, using BsmI, ApaI and TaqI endonucleases.

Results: The genotype BB of BsmI polymorphism was significantly associated with PBC (OR = 1.80 [95% CI; 1.19-2.73], p = 0.005). The association of the genotype BB was observed in Japanese (OR = 13.77, p = 0.001), and Italians (OR = 1.83, p = 0.019), respectively, although not significant in Italians after Bonferroni correction. The frequency of the B allele at the BsmI polymorphism was significantly higher in PBC patients (OR = 1.27 [95% CI; 1.02-1.59], p = 0.040).

Conclusions: The genotype 'BB' as well as 'B' allele at BsmI polymorphism of the VDR gene contribute to the risk of PBC development.

MeSH terms

  • Aged
  • Alleles
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Base Sequence
  • Case-Control Studies
  • DNA Primers / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Italy
  • Japan
  • Liver Cirrhosis, Biliary / etiology
  • Liver Cirrhosis, Biliary / genetics*
  • Liver Cirrhosis, Biliary / immunology
  • Male
  • Middle Aged
  • Polymorphism, Restriction Fragment Length*
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / immunology
  • Th1 Cells / immunology


  • DNA Primers
  • Receptors, Calcitriol