ABSTRACT
There is now growing evidence suggesting that Vitamin D is playing a critical role in modulating the innate and adaptive immune responses. Several polymorphisms have been identified in the vitamin D receptor (VDR) gene but their association with ulcerative colitis (UC) susceptibility remained controversy. In the current study, we examined the association between VDR polymorphisms and serum level of 25-hydroxyvitamin D [25(OH)D] with UC in Chinese Han population. Polymorphisms of FokI (rs2228570)/BsmI (rs1544410)/ApaI (rs7975232)/TaqI (rs731236) in the VDR gene were assessed in a case-control study comprising 404 UC patients and 612 controls. Moreover, 25(OH)D levels were measured by electro-chemiluminescence immunoassay in 75 UC patients and 120 controls. Our results suggested that BsmI polymorphism frequency was significantly lower in UC patients (P=0.028), and the frequency of AAC haplotype formed by BsmI, ApaI and TaqI was also significantly lower in UC patients (P=0.012). Moreover, FokI polymorphism was more frequently observed in patients with mild and moderate UC as compared to those with severe UC (P=0.001, P<0.001, respectively). Average 25(OH)D level was lower in UC patients than in controls (19.3±6.8 vs. 21.8±7.3ng/mL, P=0.017), and was significantly correlated with hemoglobin (ß=0.49, P<0.001), C-reactive protein (ß=-0.36, P<0.001), severity of UC (ß=-0.21, P=0.025) and FokI polymorphism (ß=-0.20, P=0.031) in UC patients. Interestingly, there was a significant correlation between FokI polymorphism and vitamin D deficiency (<20ng/mL) in UC patients (P=0.006). Together, these results supported that VDR polymorphisms and 25(OH)D level were significantly correlated with UC risk and severity in Chinese Han population.
Subject(s)
Colitis, Ulcerative/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Calcitriol/genetics , Vitamin D/analogs & derivatives , Adult , Alleles , Asian People/statistics & numerical data , Case-Control Studies , China/epidemiology , Colitis, Ulcerative/ethnology , Female , Genotype , Humans , Male , Middle Aged , Vitamin D/blood , Vitamin D/geneticsABSTRACT
BACKGROUND AND AIM: The vitamin D receptor (VDR) regulates immune responses and inflammation through binding with 1,25-dihydroxyvitamin D, the active form of vitamin D. The serum 25-hydroxyvitamin D (25(OH)D) level clinically reflects vitamin D status in the human body. We investigated the association of VDR polymorphisms and 25(OH)D levels in Chinese patients with Crohn's disease (CD). METHODS: Vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) were genotyped by SNaPshot. Serum 25(OH)D levels were measured by electro-chemiluminescence immunoassay. RESULTS: A total of 297 patients with CD and 446 controls were recruited. Compared with controls, mutant alleles and genotypes of BsmI and TaqI were less prevalent in patients with CD (all P < 0.05/4 = 0.0125). The AAC haplotype formed by BsmI, ApaI, and TaqI was also less prevalent in patients with CD (P = 0.004). Furthermore, 124 patients and 188 controls were randomly selected for measurements of 25(OH)D levels. Average 25(OH)D level was lower in patients with CD than in controls (15.46 ± 8.11 vs 21.64 ± 9.45 ng/mL, P < 0.001) and negatively linked to CD activity index (ß = -0.829, P < 0.001), platelet count (ß = -0.253, P < 0.001) and neutrophil percentage (ß = -0.136, P = 0.005) in patients with CD. The ApaI mutant genotype and vitamin D deficiency (<20 ng/mL) were independently associated with CD (P = 0.009, P < 0.001, respectively). In patients with CD, vitamin D deficiency interacted with FokI, ApaI, and TaqI mutant genotypes (P = 0.027, P = 0.024, and P = 0.040, respectively). CONCLUSIONS: Vitamin D receptor (BsmI, ApaI, and TaqI) mutations and lower 25(OH)D levels are associated with CD in Chinese patients. Moreover, VDR (FokI, ApaI, and TaqI) mutations and vitamin D deficiency may have a combined impact on CD.
