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

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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)1202-1209
Number of pages8
JournalJournal of Hepatology
Volume50
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

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Calcitriol Receptors
Biliary Liver Cirrhosis
Population
Genotype
Immunologic Factors
Gene Frequency
Restriction Fragment Length Polymorphisms
Autoimmune Diseases
Alleles
Polymerase Chain Reaction
Genes

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 journalArticle

Tanaka, A, Nezu, S, Uegaki, S, Kikuchi, K, Shibuya, A, Miyakawa, H, Takahashi, SI, Bianchi, I, Zermiani, P, Podda, M, Ohira, H, Invernizzi, P & Takikawa, H 2009, 'Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations', Journal of Hepatology, vol. 50, no. 6, pp. 1202-1209. https://doi.org/10.1016/j.jhep.2009.01.015
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. / Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations. In: Journal of Hepatology. 2009 ; Vol. 50, No. 6. pp. 1202-1209.
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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.",
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author = "Atsushi Tanaka and Saeko Nezu and Satoko Uegaki and Kentaro Kikuchi and Akitaka Shibuya and Hiroshi Miyakawa and Takahashi, {Shin ichi} and Ilaria Bianchi and Paola Zermiani and Mauro Podda and Hiromasa Ohira and Pietro Invernizzi and Hajime Takikawa",
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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

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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

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