Association of Crohn's disease with T cell immunoglobulin and mucin domain 3 gene polymorphisms in Chinese patients

Abstract

Objective: To explore the association of Crohn's disease (CD) with T cell immunoglobulin and mucin domain 3 (Tim-3) gene polymorphisms in patients of Zhejiang Han population in China. Methods: A total of 308 CD patients and 573 age- and sex-matched healthy controls were enrolled in our study. Two single nucleotide polymorphisms (SNPs) of Tim-3 (rs1036199 and rs10515746) were examined by the improved multiple ligase detection reaction technique (iMLDR). Analyses of linkage disequilibrium and haplotype were also performed by Haploview 4.2 software in all study subjects. Results: In general, the allele and genotype frequencies of Tim-3 (rs1036199 and rs10515746) were not statistically different between CD patients and the controls (all P>0.05). According to "the Montreal Classification" , CD patients were divided into different subgroups. The variant allele (C) and genotype (AC+ CC) of rs1036199 were more frequent in CD patients with penetrating diseases than in the controls (10.4% vs 1.7%, P=0.002; 20.8% vs 3.5%, P=0.023). Similar conclusions were also drawn for the variant allele (A) and genotype (CA+ AA) of rs10515746 in patients with penetrating diseases when compared with the controls (10.4% vs 2.2%, P=0.000; 20.8% vs 4.2%, P=0.033, respectively). The two SNPs of Tim-3 were in strong linkage disequilibrium (D'=1.0, r2=0.928). The haplotype (AC) formed by their wild-type alleles (A) and (C) was decreased in patients with penetrating CD compared with the controls (89.6% vs 98.3%, P=0.000). However, the haplotype (CA) formed by their variant alleles was more frequent in patients with penetrating CD than in the controls (10.4% vs 1.6%, P=0.000). Conclusions:Tim-3 (rs1036199 and rs10515746) variations might be correlated with the enhanced risk of penetrating diseases in CD patients. Furthermore, the haplotype (AC) and (CA) formed by the two SNPs might be a protective and a risky factor for penetrating CD respectively.