Association Of TNFSF15 With Crohn's Disease In China

Background and objectiveInflammatory Bowel Disease(IBD) is a kind of non-specific chronic inflammation of gut, including Crohn's Disease(CD) and Ulcerative Colitis(UC). Crohn's Disease is chronic granulomatous inflammation mainly located in terminal ileum and adjacent colon.The clinical symptoms of CD include abdominal pain, diarrhea, abdominal mass, weight loss, malnutrition and so on. The etiology and pathogenesis of CD remain unclear, which may be related to the comprehensive effects of three aspects including intestinal flora, tissue injury mediated by the abnormal immunity and genetic susceptibility. NOD2/CARD15 was confirmed as the first inherent predisposing gene of CD in 2001. A total prevalence rate of monozygotic twins is significantly higher than that of dizygotic twins in both CD(20%-50%VS 0%-7%) and UC(14%-19%VS 0%-5%) patients, which indicates that genetic factor plays an important role in the pathogenesis of IBD. In the recent years, many researches have shown that the polymorphism of IBD linked genes such as VDR, STAT6, HLA, CTLA-4, ICAM-1, NAT2, TLRs and so on has a close relationship with the incidence of IBD, nevertheless, there is discrepancy among different areas and races.In 2005, Japanese researcher first tested the polymorphism of 80,000 single nucleotide(SNPs) in the whole genome, and then found that the SNPs genotype of TNFSF15(Tumor necrosis factor superfamily,member 15) had a significant correlation with the susceptibility of CD in Japanese and European population, which was confirmed by the following researches for many times. But there are no reports about the relationship between TNFSF15 and CD in China.This research mainly focus on the relationship between TNFSF15 and CD.MethodExtract the peripheral venous blood of CD patients and healthy persons followed by extracting DNA. Design specific primers of target gene segments of the three polymorphism sites rs3810936, rs6478109, rs7848647, which are located in TNFSF15. Amplify target gene segments of DNA specimens using PCR followed by sequencing them. At last, analyze the relationship among allele polymorphism and susceptibility and subtype of disease using SPSS 13.0 analysis software.ResultThis study has 42 persons in CD group and 49 in control group, using SPSS 13.0 analysis software to analyse,we find that three of the TNFSF15 SNPs, rs3810936, rs6478109, rs7848647 showed no significant in allele frequency between the control and CD groups(35.7%,44.9%,χ2=1.581, P=0.209; 38.1%,43.9%,x2=0.624, P=0.429; 38.1%,44.9%,x2=0.861, P=0.354 respectively). The CC,CT,TT genotype frequency of rs3810936 are 45.2%,38.1%,16.7%and 30.6%,49.0%,20.4%, respectively, in CD group and control group. The aOR of rs3810936 for TT genotype in comparison to CC genotype is 1.810(95%CI 0.556-5.886, P=0.324), the aOR of rs3810936 for CT genotype in comparison to CC genotype is 1.900(95%CI 0.752-4.799, P=0.175), the aOR of rs3810936 for CT genotype in comparison to TT genotype is 0.952(95%CI 0.300-3.022, P=0.934). The GG,GA,AA genotype frequency of rs6478109 are42.9%, 38.1%,19.0%and 30.6%,51.0%,18.4%, respectively, in CD group and control group. The aOR of rs6478109 for GG genotype in comparison to AA genotype is 0.741 (95%CI 0.229-2.394, P= 0.616), the aOR of rs6478109 for GA genotype in comparison to GG genotype is 0.53 (95%CI 0.211-1.351, P=0.185), the aOR of rs6478109 for AA genotype in comparison to GA genotype is 1.389 (95%CI 1.444-4.345, P= 0.572). The CC,CT,TT genotype frequency of rs7848647 are42.9%,38.1%,19.0%and 30.6%, 49.0%,20.4%, respectively, in CD group and control group. The aOR of rs7848647 for TT genotype in comparison to CC genotype is 1.500 (95%CI 0.473-4.761, P=0.491), the aOR of rs7848647 for CT genotype in comparison to CC genotype isl.800 (95%CI 0.708-4.574, P= 0.217), the aOR of rs7848647 for CT genotype in comparison to TT genotype is 0.833 (95%CI 0.271-2.566, P= 0.751). And we characterize the haplotypes of these three polymorphisms, haplotype frequencies in cases and controls were estimated separately. In CD group and control group,both haplotype B1 (cc-gg-cc) carring the three risk alleles of rs3810936, rs6478109, rs7848647 (38.1% and 26.5%,P>0.05) and haplotype A1 (tt-aa-tt) carring the opposite alleles of three SNPs showed no significant association with CD(14.3%and 12.2%,P>0.05). According to multiple regression analysis, these three polymorphisms of TNFSF15 have no significant association with clinical subtypes,smoking,upper digestive tract and perianal involved of CD in China(P>0.05). Conclusion1. This study find that these three SNPs of TNFSF 15, rs3810936, rs6478109, rs7848647 showed no significant association with CD in Chinese Han population.2. These three polymorphisms of TNFSF 15 have no significant association with clinical subtypes of CD in Chinese Han population.3. The three SNPs of TNFSF 15, rs3810936, rs6478109 may have racial and regional difference.