Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1202-1209 |
| Number of pages | 8 |
| Journal | Journal of Hepatology |
| Volume | 50 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2009 |
| Externally published | Yes |
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Keywords
- Autoimmune disease
- Genetic polymorphism
- Single nucleotide polymorphism
- Th1 disease
ASJC Scopus subject areas
- Hepatology
Cite this
Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations. / 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.
In: Journal of Hepatology, Vol. 50, No. 6, 06.2009, p. 1202-1209.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations
AU - Tanaka, Atsushi
AU - Nezu, Saeko
AU - Uegaki, Satoko
AU - Kikuchi, Kentaro
AU - Shibuya, Akitaka
AU - Miyakawa, Hiroshi
AU - Takahashi, Shin ichi
AU - Bianchi, Ilaria
AU - Zermiani, Paola
AU - Podda, Mauro
AU - Ohira, Hiromasa
AU - Invernizzi, Pietro
AU - Takikawa, Hajime
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Autoimmune disease
KW - Genetic polymorphism
KW - Single nucleotide polymorphism
KW - Th1 disease
UR - http://www.scopus.com/inward/record.url?scp=67349255018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349255018&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2009.01.015
DO - 10.1016/j.jhep.2009.01.015
M3 - Article
VL - 50
SP - 1202
EP - 1209
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 6
ER -