title: [An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn's disease].
abstract: OBJECTIVE
  To investigate the association of Crohn's disease (CD) with vitamin D receptor (VDR) gene polymorphisms and serum 25-hydroxyvitamin D [25(OH)D] level.
  
  
  METHODS
  A total of 297 CD patients and 446 healthy controls were enrolled in our study. Four single nucleosides of VDR (Fok I, Bsm I, Apa I and Taq I) were genotyped by SNaPshot. Serum 25(OH)D levels were tested by electro-chemiluminescence immunoassay in 124 CD patients and 188 matched random controls.
  
  
  RESULTS
  By Chi-square test and Bonferroni correction, the frequencies of mutant allele (A) and mutant genotype (GA+AA) of Bsm I were significantly decreased in CD patients compared to controls [3.70% (22/594) vs 7.51% (67/892), 95% CI 0.289-0.776, P=0.002; 7.41%(22/297) vs 14.80% (66/446), 95% CI 0.277-0.765, P=0.002, respectively]. The similar results were seen for the mutant allele (C) and mutant genotype (TC+CC) of Taq I [4.21% (25/594) vs 7.62% (68/892), 95% CI 0.333-0.852, P=0.008; 8.42% (25/297) vs 14.57% (65/446), 95% CI 0.331-0.877, P=0.012]. The analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 and R software, respectively. The Bsm I, Apa I and Taq I polymorphic loci were found to be in a strong LD, and the AAC haplotype was significantly reduced in CD patients compared to controls [3.14% vs 6.46%, 95% CI 0.273-0.815, P=0.004]. The further serological analysis showed that average serum 25(OH)D level in CD patients was significantly lower than that of controls [(15.46±8.11) µg/L vs (21.64±9.45) µg/L, P<0.001]. By linear regression analysis, serum 25(OH)D levels in CD patients were negatively correlated to Crohn's disease activity index (β=-0.829, P<0.001), platelet count (β=-0.253, P<0.001) and the ratio of neutrophils (β=-0.136, P=0.005) independently, whereas positively related to erythrocyte sedimentation rate (β=0.191, P=0.001). Furthermore, logistic regression analysis was applied for establishing the models of gene-environment interaction. In result, both the mutant genotype (CA+AA) of Apa I and vitamin D deficiency (<20 µg/L) were shown to be the independent risk factors for CD (OR=7.580, 95% CI 2.983-19.261, P<0.001; OR=2.842, 95% CI 1.300-6.211, P=0.009, respectively). Besides, vitamin D deficiency in CD patients had multiplicative interactions with the mutant genotype (TC+CC) of Fok I, genotype (CA+AA) of Apa I and genotype (TC+CC) of Taq I, respectively (OR=0.419, 95% CI 0.194-0.906, P=0.027; OR=0.309, 95% CI 0.111-0.855, P=0.024; OR=5.841, 95% CI 1.082-31.538, P=0.040; respectively).
  
  
  CONCLUSIONS
  VDR (Bsm I, Apa I and Taq I) polymorphisms and serum 25(OH)D levels are significantly related to CD. Both the mutant genotype (CA+AA) of Apa I and vitamin D deficiency are independent risk factors of CD. The mutations of VDR (Fok I, Apa I and Taq I) and vitamin D deficiency might have a synergistic effect on CD susceptibility.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Xia
authors.forename: Xinxin
authors.initials: X
authors.lastname: Lin
authors.forename: Maodong
authors.initials: M
authors.lastname: Guo
authors.forename: Lijia
authors.initials: L
authors.lastname: Jiang
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Lin
authors.forename: Ran
authors.initials: R
authors.lastname: Ding
authors.forename: Shilin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Email: wzjiangyi@yeah.net.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D