The IL17F (rs763780, 7488T/C) variant was associated with an increased risk for the development of CD, and affected some clinical features of UC and CD. The IL17A (rs2275913, G-197A) variant had a weak association with the severity of UC. There was a risk haplotype in IL17A which could increase the risk of UC.
BackgroundPrevious studies implicated that IL23R and IL17 genes play an important role in autoimmune inflammation. Genome-wide association studies have also identified multiple single nucleotide polymorphisms (SNPs) in the IL23R gene region associated with inflammatory bowel diseases. This study examined the association of IL23R and IL17A gene SNPs with ulcerative colitis susceptibility in a population in China.MethodologyA total of 270 ulcerative colitis and 268 healthy controls were recruited for the analyses of 23 SNPs in the IL23R and IL17A regions. Genomic DNA was extracted and analysis of these 23 SNPs using ligase detection reaction allelic (LDR) technology. Genotype and allele associations were calculated using SPSS 13.0 software package.Principal FindingsCompared to the healthy controls, the variant alleles IL23R rs7530511, and rs11805303 showed a statistically significant difference for ulcerative colitis susceptibility (0.7% vs 3.3%, P = 0.002; 60.4% vs 53.2%, P = 0.0017, respectively). The linkage disequilibrium (LD) patterns of these SNPs were measured and three LD blocks from the SNPs of IL23R and one block from those of IL17A were identified. A novel association with ulcerative colitis susceptibility occurred in haplotypes of IL23R (Block1 H3 P = 0.02; Block2 H2 P = 0.019; Block3 H4 P = 0.029) and IL17A (H4 P = 0.034). Pair-wise analyses showed an interaction between the risk haplotypes in IL23R and IL17A (P = 0.014).ConclusionsOur study demonstrated that rs7530511, and rs11805303 of IL23R were significantly associated with ulcerative colitis susceptibility in the Chinese population. The most noticeable finding was the linkage of IL23R and IL17A gene region to ulcerative colitis risk due to the gene-gene interaction.
Objective: To use a meta-analysis approach to evaluate the efficacy and safety of purine analogues, azathioprine (AZA) and 6-mercaptopurine (6-MP), in the prevention of postoperative recurrence of Crohn's disease (CD), as compared with mesalamine or 5-aminosalicylic acid (5-ASA). Methods: The Pubmed, Cochrane Library, and Embase literature databases were searched for relevant studies with the key words "azathioprine", "6-mercaptopurine", "purine analogue", "mesalamine", or "5-ASA". The efficacy and safety of purine analogues in the retrieved randomized controlled trials (RCTs) were evaluated with RevMan 5.0.25 (The Cochrane Collaboration, Oxford, England) and STATA 12.0 (Stata Corporation, College Station, TX, USA). The outcome measures of AZA and 6-MP, compared to mesalamine and 5-ASA (control arms), were: clinical recurrence, endoscopic recurrence, and adverse event rates. Results: Five RCTs, comprised of 429 patients, were analyzed. The effect of purine analogues for preventing clinical recurrence for year 1 and 2 were similar to controls (year 1: n = 390; recurrence rate: 18.6% vs. 20.9%; RR: 0.88, 95% CI: 0.60-1.30, p = 0.53; year 2: n = 270; recurrence rate: 29.9% vs. 38.2%; RR: 0.76, 95% CI: 0.55-1.05, p = 0.10). In contrast, purine analogues were more effective than controls in preventing severe endoscopic recurrence (i2-4) for year 1 (n = 289; 32.4% vs. 46.1%; RR: 0.71, 95% CI: 0.53-0.94, p = 0.02). However, purine analogues were associated with more adverse events leading to drug withdrawal than the controls (20.1% vs. 7.9%; RR: 2.57, 95% CI: 1.47-4.51, p = 0.0010). Conclusion: Purine analogues are more effective than controls in preventing endoscopic postoperative recurrence in CD, but are associated with more adverse events.
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