Dataset Information

Lymphocyte Antigen 75 Polymorphisms Are Associated with Disease Susceptibility and Phenotype in Japanese Patients with Inflammatory Bowel Disease.

ABSTRACT: Recent genome-wide association studies have rapidly improved our understanding of the molecular pathways leading to inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). Although several reports have demonstrated that gene single nucleotide polymorphisms (SNPs) are associated with susceptibility to IBD, its precise genetic factors have not been fully clarified. Here, we performed an association analysis between lymphocyte antigen 75 (LY75) genetic variations and IBD susceptibility or phenotype. SNPs were genotyped in 51 CD patients, 94 UC patients, and 269 healthy controls of Japanese ethnicity. We detected a significant relationship with CD susceptibility for the rs16822581 LY75 SNP (P = 0.045). One haplotype (GT, P = 0.042) was also associated with CD susceptibility, while another carrying the opposite SNP (CA) was linked to an absence of surgical history for CD. Our findings confirm that LY75 is involved in CD susceptibility and may play a role in disease activity in the Japanese population.

SUBMITTER: Hirayama A

PROVIDER: S-EPMC5124651 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Lymphocyte Antigen 75 Polymorphisms Are Associated with Disease Susceptibility and Phenotype in Japanese Patients with Inflammatory Bowel Disease.

Hirayama Atsuhiro A Joshita Satoru S Kitahara Kei K Mukawa Kenji K Suga Tomoaki T Umemura Takeji T Tanaka Eiji E Ota Masao M

Disease markers 20161114

Recent genome-wide association studies have rapidly improved our understanding of the molecular pathways leading to inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). Although several reports have demonstrated that gene single nucleotide polymorphisms (SNPs) are associated with susceptibility to IBD, its precise genetic factors have not been fully clarified. Here, we performed an association analysis between lymphocyte antigen 75 (LY75</i ...[more]

PMID: 27965521

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Project description:BackgroundInflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions.MethodsCD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed.ResultsWe extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016).ConclusionsWe confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility.

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Lymphocyte Antigen 75 Polymorphisms Are Associated with Disease Susceptibility and Phenotype in Japanese Patients with Inflammatory Bowel Disease.

Publications

<i>Lymphocyte Antigen 75</i> Polymorphisms Are Associated with Disease Susceptibility and Phenotype in Japanese Patients with Inflammatory Bowel Disease.

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