Correlation between aryl hydrocarbon receptor gene polymorphisms and haplotypes and ulcerative colitis

Abstract

Objective To investigate the correlation between aryl hydrocarbon receptor (AhR) gene polymorphisms and haplotypes and susceptibility of ulcerative colitis (UC). Methods From January 2010 to October 2017, at the Second Affiliated Hospital of Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University, Central Hospital of Wenzhou City and Wenzhou People Hospital, a total of 396 UC patients were recruited as the UC group. In the same period, 573 age- and gender-matched healthy individuals were taken as the healthy control group. Three single nucleotide polymorphisms (SNP) of AhR (rs10249788, rs2066853, rs2158041) were examined by modified multiple ligase detection reaction technique. The correlation between the differences in the frequency of each SNP mutant alleles, genotypes and clinical pathological features of UC was analyzed by unconditional logistic regression analysis. Haploview 4.2 software was applied to analyze the linkage disequilibrium (LD). Results The frequency of mutant allele C and genotype TC+ CC of AhR (rs10249788) of UC group were higher than those of the healthy control group (75.00%, 594/792 vs. 69.98%, 802/1 146; 95.45%, 378/396 vs. 91.10%, 522/573), the differences were statistically significant (odds ratio (OR)=1.287, 95% confidence interval (CI) 1.049 to 1.579, P=0.016; OR=2.052, 95%CI 1.180 to 3.568, P=0.011). Compared with the patients with distal colitis, the frequencies of mutant allele C and genotype TC+ CC of AhR (rs10249788) were higher in the patients with extensive colitis (71.34%, 341/478 vs. 80.57%, 253/314; 93.31%, 223/239 vs. 98.73%, 155/157), and the differences were statistically significant (OR=1.666, 95%CI 1.183 to 2.347, P=0.003; OR=5.561, 95%CI 1.260 to 24.530, P=0.023). The results of LD analysis indicated that rs10249788 and rs2066853, rs10249788 and rs2158041, rs2066853 and rs2158041 were linked to each other (D′=0.636, 0.430 and 0.980; r2=0.270, 0.023 and 0.177). Compared with the healthy control group, the frequency of haplotype TAC of UC group decreased (20.20%, 231.5/1 146.0 vs. 16.24%, 128.6/792.0), however the frequency of haplotype CAC increased (14.43%, 165.4/1 146.0 vs. 20.47%, 162.1/792.0), and the differences were statistically significant (OR=0.767, 95%CI 0.605 to 0.973, P=0.029; OR=1.529, 95%CI 1.204 to 1.941, P<0.01). The results of further analysis demonstrated that the frequency of haplotype CGC was higher in patients with extensive colitis than that of patients with distal colitis (38.69%, 121.5/314.0 vs. 29.48%, 140.9/478.0), and the difference was statistically significant (OR=1.511, 95%CI 1.119 to 2.040, P=0.007), while the frequency of haplotype TAC in patients with extensive colitis was lower than that of patients with distal colitis (12.10%, 38/314.0 vs. 17.55%, 83.9/478.0), and the difference was statistically significant (OR=0.646, 95%CI 0.483 to 0.983, P=0.037). Conclusion AhR (rs10249788) may be a potential locus affecting susceptibility to UC, and synergistically influence the risk and the location of UC. Key words: Colitis, ulcerative; Polymorphism, genetic; Haplotypes; Aryl hydrocarbon receptor