title: Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn's disease.
abstract: OBJECTIVE
  To investigate the correlation between interleukin-18 (IL-18) gene polymorphisms and the risk of developing Crohn's disease (CD).
  
  
  METHODS
  The PubMed, CISCOM, CINAHL, Web of Science, EBSCO, Cochrane Library, MEDLINE, EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1(st), 2013. Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis. A meta-analysis was conducted using a random-effects model with STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated.
  
  
  RESULTS
  Seven case-control studies, with a total of 1930 CD cases and 1930 healthy subjects, met our inclusion criteria. The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238 G>C polymorphisms may correlate with an increased risk of CD under five genetic models (all P < 0.05). Furthermore, we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models (C allele vs A allele: OR = 2.03, 95%CI: 1.20-3.43, P = 0.008; CC vs AA+AC: OR = 2.39, 95%CI: 1.2-4.43, P = 0.006; CC vs AC: OR = 2.31, 95%CI: 1.22-4.38, P = 0.010). However, such associations were not found for the IL-18 rs917997 C>T, codon 35 A>C and rs1946519 G>T polymorphisms (all P > 0.05). A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD. Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans (all P < 0.05), but not among Caucasians (all P > 0.05).
  
  
  CONCLUSIONS
  This meta-analysis indicated that the IL-18 rs1946518 A>C, rs187238 G>C and rs360718 A>C polymorphisms may contribute to susceptibility to CD, especially among Asians and Africans. These polymorphisms are known to reduce IL-18 mRNA and protein levels.
authors.affiliation: Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People's Hospital, Yangzhou 225001, Zhejiang Province, China.
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Gao
authors.affiliation: Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People's Hospital, Yangzhou 225001, Zhejiang Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People's Hospital, Yangzhou 225001, Zhejiang Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People's Hospital, Yangzhou 225001, Zhejiang Province, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People's Hospital, Yangzhou 225001, Zhejiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People's Hospital, Yangzhou 225001, Zhejiang Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Su-Jun Gao, Li Zhang, Wei Lu, Lu Wang, Lei Chen, Zhen Zhu, Hai-Hang Zhu, Department of Gastroenterology, Subei People's Hospital, Yangzhou 225001, Zhejiang Province, China.
authors.forename: Hai-Hang
authors.initials: HH
authors.lastname: Zhu
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D016014:Linear Models; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C000589760:IL18 protein, human; D020382:Interleukin-18
keywords: Crohn’s disease; Interleukin-18; Meta-analysis; Single nucleotide polymorphism