Yonsei Med J.  2016 Jan;57(1):153-164. 10.3349/ymj.2016.57.1.153.

Association between Toll-Like Receptor 9-1237T/C Polymorphism and the Susceptibility of Inflammatory Bowel Diseases: A Meta-Analysis

Affiliations
  • 1Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China. bingxia@aliyun.com
  • 2The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, P.R. China.

Abstract

PURPOSE
The -1237T/C polymorphism of the Toll-like receptor 9 (TLR9) gene has been implicated in the susceptibility of inflammatory bowel diseases (IBDs), but the results remain conflicting. We further investigated this association via meta-analysis.
MATERIALS AND METHODS
Multiple electronic databases were extensively searched until February, 2015. The strength of association was evaluated by calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
A total of 2987 cases and 2388 controls from eight studies were analyzed. Overall, association was found between TLR9 -1237T/C polymorphism and the risk of IBDs when all the studies were pooled (recessive model, OR: 1.59, 95% CI: 1.02-2.47, p=0.04; homozygote comparison, OR: 1.62, 95% CI: 1.04-2.52, p=0.03; allele model, OR: 1.13, 95% CI: 1.00-1.27, p=0.05). Stratification by ethnicity indicated an association between TLR9 -1237T/C polymorphism and IBDs risk in Caucasians (recessive model, OR: 1.59, 95% CI: 1.02-2.47, p=0.04; homozygote comparison, OR: 1.62, 95% CI: 1.04-2.52, p=0.03; allele model, OR: 1.12, 95% CI: 1.00-1.27, p=0.05). When stratified by disease type, significant correlation were only found in the Crohn's disease subgroup (recessive model, OR: 1.69, 95% CI: 1.05-2.73, p=0.03; homozygote model, OR: 1.74, 95% CI: 1.07-2.82, p=0.02; allele model, OR: 1.15, 95% CI: 1.01-1.32, p=0.04).
CONCLUSION
The present study suggested that the TLR9 -1237T/C polymorphism might act as a risk factor in the development of IBDs, particularly in Caucasians.

Keyword

Toll-like receptor 9; -1237T/C; polymorphism; inflammatory bowel disease; meta-analysis

MeSH Terms

Alleles
European Continental Ancestry Group/genetics
Genetic Predisposition to Disease/*genetics
Homozygote
Humans
Inflammatory Bowel Diseases/ethnology/*genetics
Odds Ratio
Polymorphism, Genetic/*genetics
Risk Factors
Toll-Like Receptor 9/*genetics/metabolism
Toll-Like Receptor 9

Figure

  • Fig. 1 Flow chart of literature retrieval in our meta-analysis.

  • Fig. 2 Forest plots for the meta-analysis of the association between TLR9 -1237T/C polymorphism and the susceptibility of IBDs. (A) Recessive model. (B) Homozygote comparison. (C) Allele model. CI, confidence interval; IBD, inflammatory bowel disease.

  • Fig. 3 Forest plot for the meta-analysis of the association between TLR9 -1237T/C polymorphism and the susceptibility of IBDs stratified by ethnicity (recessive model). CI, confidence interval; IBD, inflammatory bowel disease.

  • Fig. 4 Forest plot for the meta-analysis of the association between TLR9 -1237T/C polymorphism and the susceptibility of IBDs stratified by ethnicity (homozygote comparison). CI, confidence interval; IBD, inflammatory bowel disease.

  • Fig. 5 Forest plots for the meta-analysis of the association between TLR9 -1237T/C polymorphism and the susceptibility of IBD stratified by ethnicity (allele model). CI, confidence interval; IBD, inflammatory bowel disease.

  • Fig. 6 Forest plot for the meta-analysis of the association between TLR9 -1237T/C polymorphism and the susceptibility of IBDs stratified by clinical type (recessive model). CI, confidence interval; IBD, inflammatory bowel disease; CD, Crohn's disease; UC, ulcerative colitis.

  • Fig. 7 Forest plot for the meta-analysis of the association between TLR9 -1237T/C polymorphism and the susceptibility of IBDs stratified by clinical type (homozygote comparison). CI, confidence interval; IBD, inflammatory bowel disease; CD, Crohn's disease; UC, ulcerative colitis.

  • Fig. 8 Forest plot for the meta-analysis of the association between TLR9 -1237T/C polymorphism and the susceptibility of IBDs stratified by clinical type (allele model). CI, confidence interval; IBD, inflammatory bowel disease; CD, Crohn's disease; UC, ulcerative colitis.

  • Fig. 9 Funnel plots for TLR9 -1237T/C polymorphism and IBDs: (A) dominant model, (B) recessive model, (C) heterozygote comparison, (D) homozygote comparison, and (E) allele model. Each point represents a separate study for the indicated association. SE, standardized effect; IBD, inflammatory bowel disease; OR, odds ratio.


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