Association of decoy receptors and osteoprotegerin gene polymorphisms with susceptibility and clinical phenotypes of Crohn′s disease

Abstract

Objective To investigate the correlation between decoy receptor (DcR)1, DcR2, osteoprotegerin (OPG) gene polymorphisms and susceptibility of Crohn′s disease (CD) in Han population in Zhejiang province. Methods From April 2008 to July 2017, at the Department of Gastroenterology of The Second Affiliated Hospital of Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, Central Hospital of Wenzhou and Renmin Hospital of Wenzhou, 285 patients diagnosed as having CD were enrolled, and during the same period 572 healthy individuals who received health checkup at the Second Affiliated Hospital of Wenzhou Medical University were collected as healthy control. The single nucleotide polymorphism (SNP) of DcR1 (rs12549481), DcR2 (rs1133782) and OPG (rs3102735) were examined by SNaPshot technique. An unconditional logistic regression analysis was performed to analyze the differences in each SNP mutation alleles and genotype frequencies between CD group and control group. Furthermore, their correlation with clinicopathological features of CD and the efficacy of corticosteroid and infliximab was also evaluated. Results The frequencies of mutant allele A and genotype GA+ AA of DcR2 (rs1133782) of CD group were 11.93% (68/570) and 22.81% (65/285), respectively, which were higher than those of healthy control group (8.22%, 94/1 144; and 15.91%, 91/572; odds ratio (OR)=1.513, 95% confidence interval (CI) 1.088 to 2.104, P=0.013; OR=1.562, 95%CI 1.094 to 2.230, P=0.014). However there was no statistically significant difference in the mutant allele and genotype frequencies of DcR1 (rs12549481) and OPG (rs3102735) between two groups (all P>0.05). The frequencies of mutant allele C and genotype TC+ CC of DcR1 (rs12549481) in patients with stricturing CD were 13.89% (25/180) and 27.78% (25/90), respectively, which were lower than those of patients with non-stricturing, non-penetrating CD (27.68%, 62/224 and 48.21%, 54/112), and the differences were statistically significant (OR=0.421, 95%CI 0.252 to 0.705, P=0.001; OR=0.413, 95%CI 0.229 to 0.747, P=0.003). Besides, the frequencies of mutant allele A and genotypes GA+ AA of DcR2 in patients with penetrating CD were 7.23% (12/166) and 13.25% (11/83), which were lower than those of patients with non-stricturing, non-penetrating CD (15.62%, 35/224 and 30.36%, 34/112), and the differences were statistically significant (OR=0.407, 95%CI 0.205 to 0.809, P=0.009; OR=0.350, 95%CI 0.165 to 0.743, P=0.005). In addition, there was no statistically significant difference in the frequencies of mutant allele and genotypes of OPG (rs3102735) among subtypes of CD with different features (all P>0.012 5). Moreover, the DcR1 (rs12549481), DcR2 (rs1133782) and OPG (rs3102735) polymorphisms were not correlated with the efficacy of corticosteroid and infliximab (all P>0.05). Conclusions DcR1 (rs12549481) mutation may be correlated with stricturing CD. DcR2 (rs1133782) mutation may be correlated with CD, especially with penetrating CD. However, the gene polymorphism of OPG (rs3102735) is not correlated with the risk of CD susceptibility. And the above gene SNP may be independent of the efficacy of corticosteroid and infliximab. Key words: Crohn disease; Polymorphism, single nucleotide; Decoy receptor; Osteoprotegerin