Identification of the polymorphisms in IFITM1 gene and their association in a Korean population with ulcerative colitis

Abstract

Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFNs and cellular anti-proliferative activities. We previously showed that the IFITM3 single nucleotide polymorphisms (SNPs) associated with susceptibility to ulcerative colitis (UC). The present study aimed to investigate whether the polymorphisms in the IFITM1 gene are associated with susceptibility to UC. We also evaluated the expression levels in the putative functional promoter polymorphisms to determine the change of their activity. Gene expression profiles in the tissues obtained from human digestive tracts by RT-PCR, and the possible variation sites and SNPs of IFITM1 were identified by direct sequencing method. Genotype analysis in the IFITM1 SNPs was performed by high resolution melting and TaqMan probe analysis, and the haplotype frequencies of IFITM1 SNPs for multiple loci were estimated using the expectation maximization (EM) algorithm. The expression levels in the putative functional promoter polymorphisms were evaluated by performing a luciferase reporter assay. We identified two SNPs and two variation sites, g.-1920G>A (rs77537847), g.-1547delA (novel) and g.-416C>G (rs11246062) in the promoter region, and g.364delA (rs200576757) in intron 1. The genotype and allele frequencies of the g.-1920G>A polymorphism of IFITM1 gene in the UC patients were significantly different from those of the healthy controls (P=0.002 and 0.042, respectively). These results suggest that the g.-1920G>A polymorphism in IFITM1 may be associated with susceptibility to UC.

The IFITM protein family in adaptive immunity

“…Recent studies have identified new roles for the IFITM family in Th differentiation and atopic and inflammatory disease, which are independent of their functions in cellular resistance to viral infection. 13,36,[80][81][82] Mouse studies showed that while IFITM deficiency was protective against induction of Th2 immune pathology and asthma, 13 it exacerbated Th17-driven inflammation in colitis, 82 highlighting the context dependency of their impact on inflammation. Clearly, further studies will be required to investigate the contribution of the different family members to the immune response and inflammation, and the cellular and molecular mechanisms that underlie their functions.…”

“…78 Likewise, their expression is up-regulated in inflamed mucosa of ulcerative colitis and Crohn's disease patients, 43,79 and polymorphisms in IFITM1 and IFITM3 are associated with increased susceptibility to ulcerative colitis. 80,81 In mice, the IFITM family protect against colitis. 82 IFITM3 deficiency led to exacerbation of chemical-induced colitis, with increased infiltration of macrophages and effector T cells to the colon lamina propria, and biased CD4 + Th differentiation to Th17.…”

The anti‐inflammatory IFITM genes ameliorate colitis and partially protect from tumorigenesis by changing immunity and microbiota

“…In addition, due to their altered expression in transformed tissues, IFITM genes are overexpressed in colitis‐associated colon cancer and in severely inflamed mucosa of UC and CD patients . Furthermore, polymorphism in the IFITM3 and IFITM1 genes was found to be associated with susceptibility to UC …”

Identification of the Polymorphisms in IFITM2 and IFITM5 Genes and their Association with Ulcerative Colitis

“…The NOD2 gene, which has been widely shown to influence both the susceptibility and phenotype of patients with CD, is located at the IBD1 locus [3,8,18]. We previously reported that an exon 4 variation of the Tim-1 gene and the SNPs of the IL27, TNFRSF17 and EED genes were associated with UC in a Korean population [5,6,9,19].…”