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

作者：Tanaka Atsushi^*; Nezu Saeko; Uegaki Satoko; Kikuchi Kentaro; Shibuya Akitaka; Miyakawa Hiroshi; Takahashi Shin ichi; Bianchi Ilaria; Zermiani Paola; Podda Mauro; Ohira Hiromasa; Invernizzi Pietro; Takikawa Hajime

来源：Journal of Hepatology, 2009, 50(6): 1202-1209.

DOI：10.1016/j.jhep.2009.01.015

• Genetic polymorphism
• Autoimmune disease
• Single nucleotide polymorphism
• Th1 disease

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.

• 出版日期2009-6