Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations.
OBJECTIVE
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.
Tanaka
Atsushi
A
Department of Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan. a-tanaka@med.teikyo-u.ac.jp
Nezu
Saeko
S
Uegaki
Satoko
S
Kikuchi
Kentaro
K
Shibuya
Akitaka
A
Miyakawa
Hiroshi
H
Takahashi
Shin-ichi
S
Bianchi
Ilaria
I
Zermiani
Paola
P
Podda
Mauro
M
Ohira
Hiromasa
H
Invernizzi
Pietro
P
Takikawa
Hajime
H
D000368:Aged; D000483:Alleles; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D007564:Japan; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D017931:DNA Primers; D018167:Receptors, Calcitriol