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[An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn's disease].
Zhonghua Nei Ke Za Zhi. 2015 Jul; 54(7):601-6.ZN

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+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableDepartment of Gastroenterology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Email: wzjiangyi@yeah.net.

Pub Type(s)

Journal Article

Language

chi

PubMed ID

26359022

Citation

Xia, Shenglong, et al. "[An Analysis of Vitamin D Receptor Gene Polymorphisms and Serum 25-hydroxyvitamin D Levels in Patients With Crohn's Disease]." Zhonghua Nei Ke Za Zhi, vol. 54, no. 7, 2015, pp. 601-6.
Xia S, Lin X, Guo M, et al. [An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn's disease]. Zhonghua Nei Ke Za Zhi. 2015;54(7):601-6.
Xia, S., Lin, X., Guo, M., Jiang, L., Jin, J., Lin, X., Ding, R., Li, S., & Jiang, Y. (2015). [An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn's disease]. Zhonghua Nei Ke Za Zhi, 54(7), 601-6.
Xia S, et al. [An Analysis of Vitamin D Receptor Gene Polymorphisms and Serum 25-hydroxyvitamin D Levels in Patients With Crohn's Disease]. Zhonghua Nei Ke Za Zhi. 2015;54(7):601-6. PubMed PMID: 26359022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn's disease]. AU - Xia,Shenglong, AU - Lin,Xinxin, AU - Guo,Maodong, AU - Jiang,Lijia, AU - Jin,Jie, AU - Lin,Xiuqing, AU - Ding,Ran, AU - Li,Shilin, AU - Jiang,Yi, PY - 2015/9/12/entrez PY - 2015/9/12/pubmed PY - 2015/11/15/medline SP - 601 EP - 6 JF - Zhonghua nei ke za zhi JO - Zhonghua Nei Ke Za Zhi VL - 54 IS - 7 N2 - 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. SN - 0578-1426 UR - https://www.unboundmedicine.com/medline/citation/26359022/[An_analysis_of_vitamin_D_receptor_gene_polymorphisms_and_serum_25_hydroxyvitamin_D_levels_in_patients_with_Crohn's_disease]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0578-1426&amp;year=2015&amp;vol=54&amp;issue=7&amp;fpage=601 DB - PRIME DP - Unbound Medicine ER -