[Associations of ulcerative colitis with vitamin D receptor gene polymorphisms and serum levels of 25-hydroxyl vitamin D].

OBJECTIVE: To explore the associations of ulcerative colitis (UC) with vitamin D receptor (VDR) gene polymorphisms and serum levels of 25-hydroxyl vitamin D[25(OH)D].

METHODS: From July 2004 to July 2013, a total of 404 UC patients were recruited from 4 hospitals of Wenzhou City. A total of 612 controls were collected from Health Examination Center of Second Affiliated Hospital of Wenzhou Medical University. Four single nucleotide polymorphisms of VDR (Fok I, Bsm I, Apa I, Taq I) were detected by mini-sequencing technique. The frequencies of minor allele and genotype of VDR were compared between UC patients and the controls by χ(2) test and Bonferroni correction. Moreover, 75 UC patients and 120 gender-and age-matched healthy controls during the corresponding period were randomly selected for determining the serum levels of 25(OH)D by electrochemiluminescence immunoassay and were compared by Student's test.

RESULTS: After Bonferroni correction, mutant allele and genotype frequencies of VDR (Fok I, Bsm I, Apa I, Taq I) did not statistically differ between UC patients and the controls (all P > 0.012 5). Stratification by the Truelove & Witts severity index, mutant allele (C) and genotype (TC+CC) of VDR(Fok I) were significantly higher in patients with mild and moderate UC than in those with severe UC (54.37% (373/686) vs 37.70% (46/122), 81.92% (281/343) vs 55.74% (34/61), both P < 0.01). Haplotype analysis showed that three polymorphic loci of Bsm I, Apa Iand Taq Iwere in a complete linkage disequilibrium. The AAC haplotype decreased significantly in UC patients compared to the controls (3.58% (29/808) vs 6.01% (74/1 224), P = 0.012). The average serum levels of 25 (OH)D in UC patients were significantly lower than those in the controls ((48 ± 17) vs (54 ± 18)nmol/L, P = 0.017). Furthermore, the average serum levels of 25(OH)D were significantly higher in patients with mild and moderate UC than in those with severe UC and were significantly lower in patients with extensive colitis than in those with distal colitis (both P < 0.01). By linear regression analysis, the serum levels of 25(OH)D in UC patients were independently and positively correlated with hemoglobin (β = 0.499, P < 0.01) and yet independently and negatively correlated with C-reaction protein (β = -0.346, P < 0.01) and white blood cells (β = -0.291, P = 0.002). Using Logistic regression analysis, it was found that mutant genotype (GA/AA) of VDR (Bsm I) played an independently protective role in UC (OR = 0.328, P = 0.028) while mutant genotype (TC/CC) of VDR (Fok I) and vitamin D deficiency (<50.0 nmol/L) had an interaction in UC (OR = 2.070, P = 0.006).

CONCLUSIONS: Genetic polymorphism of VDR (Fok I, Bsm I, Apa I, Taq I) and serum levels of 25(OH)D are significantly correlated with UC. Mutation of VDR (Bsm I) is a protective factor for UC. Moreover, mutant genotype (TC/CC) of VDR (Fok I) and vitamin D deficiency may exert synergistic effects on the susceptibility to UC.