title: [Associations of Crohn's disease with DR4 and DR5 gene polymorphisms].
abstract: OBJECTIVE
  To assess the associations of death receptor DR4 and DR5 gene polymorphisms with Crohn's disease (CD).
  
  
  METHODS
  A total of 295 CD patients and 490 healthy controls were recruited. Three single nucleotide polymorphisms (SNPs) of the DR4 (rs13278062, rs20575) and DR5 (rs1047266) genes were determined with a SNaPshot method. Unconditional logistic regression analysis was carried out for determining the allelic and genotypic differences of the three SNPs between CD patients and the controls, as well as the influence of the DR4 and DR5 gene polymorphisms on the clinical features of CD patients. Linkage disequilibrium and haplotype analysis were calculated by haplotype 4.2 and R language software. A gene-gene interaction model was established to analyze whether the three SNPs can exert a synergistic effect on the susceptibility to CD.
  
  
  RESULTS
  The mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were increased among CD patients compared to the controls (37.12% vs. 32.04%, P = 0.040, 95%CI: 1.010-1.550; 62.71% vs. 54.90%, P = 0.032, 95%CI: 1.028-1.855, respectively). However, the allelic and genotypic frequencies of DR4 (rs20575) and DR5 (rs1047266) did not differ between the two groups (all P > 0.05). Based on the Montreal Classification Standards, the CD patients were stratified by locations and behaviors of the disease. After multiple comparison correction (P < 0.0125), compared to ileocolonic CD patients respectively, the mutant allele (T) and genotype (GT+TT) of the rs13278062 polymorphism were significantly increased in colonic CD patients (41.04% vs. 25.64%, P = 0.002, 95%CI: 0.315-0.778; 66.04% vs. 41.03%, P = 0.001, 95%CI: 0.196-0.655, respectively) and terminal ileum CD patients (41.44% vs. 25.64%, P = 0.002, 95%CI: 0.311-0.762; 74.77% vs. 41.03%, P < 0.001, 95%CI: 0.126-0.437, respectively). In comparison to penetrating CD patients, the mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were significantly decreased in stricturing CD patients (32.29% vs. 48.91%, P = 0.007, 95%CI: 0.300-0.828; 57.29% vs. 86.96%, P = 0.001, 95%CI: 0.078-0.520, respectively). A similar conclusion was drawn for the mutant genotype (GT+TT) of DR4 (rs13278062) in non-stricturing, non-penetrating CD patients (58.82% vs. 86.96%, P = 0.001, 95%CI: 0.086-0.536). Haplotype analysis indicated that the CT haplotype formed by rs20575 and rs13278062 was increased in CD patients compared to the controls (37.1% vs. 31.8%, P = 0.029, OR=1.279, 95%CI: 1.022-1.600). The outcome of a gene-gene interaction model indicated that the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may play a negatively synergistic role in CD patients (B = - 0.483, OR = 0.617, P = 0.030).
  
  
  CONCLUSIONS
  The rs13278062 polymorphism of the DR4 gene not only can confer an increased risk for CD, but may also influence the location of the lesions and the disease behaviors. The CT haplotype formed by rs20575 and rs13278062 may be an independent risk factor for CD. Furthermore, the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may exert a negative synergistic effect on CD.
authors.affiliation: Department of Gastroenterology, Department of Infectious Disease, the Second Affiliated Hospital, Department of Gastroenterology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China. Email: wzjiangyi@yeah.net.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Lin
authors.forename: Lingxiang
authors.initials: L
authors.lastname: Jin
authors.forename: Chenwei
authors.initials: C
authors.lastname: Pan
authors.forename: Shuzi
authors.initials: S
authors.lastname: Zheng
authors.forename: Daguan
authors.initials: D
authors.lastname: Zhang
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Lin
authors.forename: Ran
authors.initials: R
authors.lastname: Ding
authors.forename: Lijia
authors.initials: L
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human