The Relationgship Between The VDR Gene Polymorphism, HBD And Ulcerative Colitis

Background and purposeUlcerative colitis (UC) is a chronic inflammation of the intestine. The etiopathogenesis of UC has not been clearly elucidated, however, its development is influenced by genetic, environmental and immunological factors.In its place UC is considered to be complex polygenic diseases. Several studies have demonstrated the identification of 20 gene locus located on chromosome 1-19 as a susceptibility gene in UC.Vitamin D is an important immune system regulator and antimicrobial. Many data identify vitamin D as a key regulator of gastrointestinal homeostasis and an important player in regulation of the innate immune response.These effects of vitamin D are thought to be mediated through the Vitamin D receptor(VDR), located on chromosome 12. Several polymorphic sites were found on the VDR gene, such as Fok I, Bsm I, Apa I, Taq I, poly (A) and Cdx2. The study found that VDR gene polymorphism has been associated with increased susceptibility to UC in overseas patients, but have not study in Chinese patients.Human bata-defensin (hBD) are antimicrobial peptides secreted by endothelial cells in intestinal tract as a component of the innate host defence. In the gastrointestinal tract, these peptides have bactericidal activity. This antimicrobial quality allows defensins to protect the host epithelium and stem cells from virulent pathogens and also help to regulate the number and composition of commensal microbiotal. The relationship between gut inflammation and the timing of defensin deficiency is unclear. There was not study about VDR and defensin at the same time. This study was designed to determine if polymorphisms of the VDR gene are associated with UC susceptibility in within north China Han people. Meanwhile, to offer the evidence of genetic mechanism in UC.Methods A total of 218 UC patients and 251 healthy controls were genotyped for VDR gene polymorphisms (Apa I, Taq I, Bsm I and Fok I) using PCR-RFLP assay. To study of expression of VDR mRNA,hBD-1 mRNA and hBD-2 mRNA in epithelial tissue of 30 patients with active UC and 32 controls using Real-time PCR assay. Results Among the four examined VDR gene polymorphisms, the Bsm I polymorphism showed a slightly higher distribution in our study population than that of previous studies. The increased frequency of the Bb genotype of the Bsm I VDR gene polymorphism was associated with UC as compared to healthy controls (28.4% vs.18.7%χ2=6.044, P=0.014, OR=1.739,95% CI=1.122-2.697). Moreover, Bsm I polymorphic allele (B) frequency was significantly increased in the UC cases, as compared to the healthy controls (14.7% vs.7.8%χ2=6.222, P=0.013; OR=1.670,95% CI=1.113-2.506). The other three VDR gene polymorphisms (Apa I, Taq I, and Fok I) were not associated with UC susceptibility. None of these four VDR polymorphisms had statistical association with clinicopatholgical parameters of these UC patients.The express of VDR mRNA and hBD-2 mRNA incresed in active UC mucosa compared with normal mucosa (P<0.05). However, the express of hBD-1 mRNA was not statistically significant in two groups.Conclusion This study demonstrated a probable association of the Bsm I polymorphism of the VDR gene with ulcerative colitis susceptibility in Han Chinese. None of VDR polymorphisms had statistical association with clinicopatholgical parameters of these UC patients. The mechanism of VDR gene may be increasing the expression of hBD-2 mRNA in occurrence of UC.