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
Department of Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
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.
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.
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).
The genotype 'BB' as well as 'B' allele at BsmI polymorphism of the VDR gene contribute to the risk of PBC development.
背景/目的：维生素D受体（VDR）激动剂最近被确定为能够抑制Th1介导的免疫反应的强效免疫调节剂，这使我们考虑功能性VDR多态性可能会增加原发性胆汁性肝硬化（PBC，一种Th1介导的自身免疫性疾病）发病风险的假说。在本研究中，我们旨在阐明VDR多态性与日本和意大利人群中PBC易感性的遗传关联。
我们纳入了334例PBC患者（195例日本人，139例意大利人）以及334例年龄和性别匹配的对照（179例日本人，156例意大利人）。使用BsmI、ApaI和TaqI核酸内切酶通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行VDR基因分型。
BsmI多态性的BB基因型与PBC显著相关（比值比[OR]=1.80[95%置信区间（CI）：1.19-2.73]，p=0.005）。BB基因型的关联分别在日本人（OR=13.77，p=0.001）和意大利人（OR=1.83，p=0.019）中观察到，尽管在意大利人经Bonferroni校正后不显著。PBC患者中BsmI多态性的B等位基因频率显著更高（OR=1.27[95%CI：1.02-1.59]，p=0.040）。
VDR基因BsmI多态性的“BB”基因型以及“B”等位基因会增加PBC发病风险。
