Relationship between gene polymorphisms of T cell immunoglobulin domain and mucin domain protein-3 and ulcerative colitis

Abstract

Objective To investigate the relationship between gene polymorphisms of T cell immunoglobulin domain and mucin domain protein-3 (Tim-3) and ulcerative colitis (UC) in Han nationality of Zhejiang. Methods A total of 391 UC patients and 573 healthy controls were recruited. Two single nucleotide polymorphisms (SPNs) of Tim-3 (rs1036199 and rs10515746) were examined by the improved multiple ligase detection reaction technique. Chi-square test or Fisher′s exact test was performed to analyze the differences in the distribution of Tim-3 gene polymorphisms and its influence on the location and severity. Haploview 4.2 software was used to analyze linkage disequilibrium (LD) and haplotype. Results The frequencies of genotype CA+ AA and mutant allele A of rs10515746 in UC were lower than those in healthy controls (1.79%, 7/391 vs 4.19%, 24/573; 0.90%, 7/782 vs 2.18%, 25/1 146; χ2= 4.295 and 4.712, P=0.038 and 0.030). However, there was no significant differences in frequencies of genotype CA+ CC and mutant allele C of gene rs1036199 between UC patients and the healthy controls (1.79%, 7/391 vs 3.49%, 20/573; 0.90%, 7/782 vs 1.74%, 20/1 146; both P>0.05). The frequencies of genotype CA+ AA and mutant allele A of rs10515746 in mild and moderate UC patients were both higher than those in severe UC patients (2.87%, 7/244 vs 0; 1.43%, 7/488 vs 0), and the differences were statistically significant (Fisher′s exact test, P=0.049 and 0.048). The analysis for LD indicated that rs1036199and rs10515746 were close LD (D′=0.92, r2=0.72). Furthermore, the frequency of haplotype CA formed by the mutant alleles C and A of these two SNPs was lower in UC patients than that in healthy controls (0.64%, 5/782 vs 1.74%, 20/1 146), and the difference was statistically significant (χ2=4.441, P=0.035). Conclusions Tim-3 (rs10515746) gene mutation may not only decrease the incidence, but also reduce the severity of UC. Moreover, the haplotype CA formed by the mutant alleles of rs1036199 and rs10515746 may also reduce the incidence of UC. Key words: T cell immunoglobulin domain and mucin domain protein-3; Colitis, ulcerative; Gene; Polymorphism, single nucleotide