Association between cytokine gene polymorphisms and ankylosing spondylitis susceptibility: a systematic review and meta-analysis.

PURPOSE OF THE STUDY: The aim of this study was to perform a meta-analysis to derive precise estimation of the association of interleukin-23 receptor (IL-23R), IL-1 receptor 2 (IL-1R2), IL-12 beta (IL-12B), IL-10 and tumour necrosis factor (TNF)-α polymorphisms with ankylosing spondylitis (AS) susceptibility. STUDY DESIGN: A systematic literature search was conducted to identify the relevant studies. Pooled OR with 95% CI was calculated to assess the strength of the association in a fixed or random-effects model. RESULTS: A total of 13 917 cases and 19 849 controls in 43 eligible studies were included in the meta-analysis. Seventeen single-nucleotide polymorphisms (SNPs) in the abovementioned five cytokine genes were evaluated. The results indicate that the nine SNPs (rs11209026, rs1004819, rs10489629, rs11465804, rs1343151, rs11209032, rs1495965, rs7517847, rs2201841) of IL-23R are associated with AS susceptibility in all study subjects in the allelic model. Moreover, stratification by ethnicity identified a significant association between seven SNPs of IL-23R and AS susceptibility in Europeans and Americans, but not in Asians. In addition, the IL-10-819 C/T and TNF-α-857 C/T polymorphisms also confer susceptibility to AS, especially in Asian population. CONCLUSION: The results suggested that the genetic susceptibility for AS is associated with the nine SNPs of IL-23R in overall population. In the subgroup analysis, significant associations were shown in European and American population, but not in Asian population. Our results also suggest that IL-10-819 C/T and TNF-α-857 C/T polymorphism might be associated with AS risk, especially in Asian population.

Associations between CD24 gene polymorphisms and inflammatory bowel disease: A meta-analysis.

AIM: To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The PubMed, Web of Science and Cochrane Library databases were searched (up to May 30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis", "IBD", "CD" or "UC"; and "polymorphism", "mutation" or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed. Stata SE12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T (rs8734) and TG1527del (rs3838646), in the CD24 gene were assessed. RESULTS: A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD (all P > 0.05). However, in a disease subgroup analysis, we found that the CD24 C170T polymorphism was associated with an increased risk of UC in a dominant model (OR = 1.79, 95%CI: 1.15-2.77, P = 0.009) and an additive model (OR = 1.87, 95%CI: 1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570del polymorphism was significantly associated with CD in the additive model (OR = 1.24, 95%CI: 1.01-1.52, P = 0.037). CONCLUSION: Our findings provide evidence that the CD24 C170T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527del polymorphism might be associated with the risk of CD.

Five-year follow-up of 263 cases of functional bowel disorder.

AIM: To determine the mortality associated with functional bowel disorders (FBDs) and their possible relationship with organic bowel disease. METHODS: Patients who satisfied the Rome III criteria for FBD (retrospective diagnosis) were followed up by telephone interview and/or outpatient review at 5 years after their first attendance. The patients were divided into the following groups: irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea and unspecified FBD. The survival of the FBD patients overall and of those with each FBD were compared with data obtained from the Guangzhou population in 2005. The incidences of colonic cancer overall and for each FBD were compared with data from the Chinese population obtained from 56 cancer registries in 19 provinces of the country in 2008. RESULTS: Two hundred and sixty-three patients were followed-up. Five patients died, which was not significantly different from the expected survival rate. No differences in mortality among the FBDs were found. There were nine cases of organic bowel disease: three colonic cancers and six colonic polyps. The incidence of colonic cancer in FBD patients was higher than that in the general Chinese population (0.23% vs 0.03%, P < 0.05). There were significant differences in the incidence of colonic cancer among the FBDs (0/134, 0/24, 2/29, 1/66, 0/10, respectively, P < 0.05); functional constipation was the most common. The incidence of colonic polyps was similar among the FBDs. The baseline age of patients who died was greater than that of those who survived (66.60 ± 6.84 years vs 45.14 ± 10.34 years, P < 0.05). The baseline age of patients who had colonic cancer or polyps during follow-up was greater than that of those without colonic cancer or polyps (60.33 ± 1.53 years vs 45.38 ± 10.62 years; 54.50 ± 6.47 years vs 45.34 ± 10.68 years, P < 0.05). CONCLUSION: FBDs do not increase the risk of death. The incidence of colonic cancer in patients with FBDs may be increased, especially in those with functional constipation and in the elderly.