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Peripheral blood methylation profiling of female Crohn's disease patients.

ABSTRACT: Crohn's disease (CD) is a chronic inflammatory disorder belonging to the inflammatory bowel diseases (IBD). CD affects distinct parts of the gastrointestinal tract, leading to symptoms including diarrhea, fever, abdominal pain, weight loss, and anemia. The aim of this study was to assess whether the DNA methylome of peripheral blood cells can be associated with CD in women.Samples were obtained from 18 female patients with histologically confirmed ileal or ileocolic CD and 25 healthy age- and gender-matched controls (mean age and standard deviation: 30.5?±?6.5 years for both groups). Genome-wide DNA methylation was determined using the Illumina HumanMethylation 450k BeadChip.Our analysis implicated 4287 differentially methylated positions (DMPs; corrected p?

SUBMITTER: Li Yim AYF

PROVIDER: S-EPMC4897922 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Peripheral blood methylation profiling of female Crohn's disease patients.

Li Yim Andrew Y F AYF Duijvis Nicolette W NW Zhao Jing J de Jonge Wouter J WJ D'Haens Geert R A M GRAM Mannens Marcel M A M MMAM Mul Adri N P M ANPM Te Velde Anje A AA Henneman Peter P

Clinical epigenetics 20160608

<h4>Background</h4>Crohn's disease (CD) is a chronic inflammatory disorder belonging to the inflammatory bowel diseases (IBD). CD affects distinct parts of the gastrointestinal tract, leading to symptoms including diarrhea, fever, abdominal pain, weight loss, and anemia. The aim of this study was to assess whether the DNA methylome of peripheral blood cells can be associated with CD in women.<h4>Methods</h4>Samples were obtained from 18 female patients with histologically confirmed ileal or ileo ...[more]

PMID: 27279921

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Project description:AimTo investigate disease-specific gene expression profiles of peripheral blood mononuclear cells (PBMCs) from Crohn's disease (CD) patients in clinical remission.MethodsPatients with CD in clinical remission or with very low disease activity according to the Crohn's disease activity index were genotyped regarding nucleotide-binding oligomerization domain 2 (NOD2), and PBMCs from wild-type (WT)-NOD2 patients, patients with homozygous or heterozygous NOD2 mutations and healthy donors were isolated for further analysis. The cells were cultured with vitamin D, peptidoglycan (PGN) and lipopolysaccharide (LPS) for defined periods of time before RNA was isolated and subjected to microarray analysis using Clariom S assays and quantitative real-time PCR. NOD2- and disease-specific gene expression profiles were evaluated with repeated measure ANOVA by a general linear model.ResultsEmploying microarray assays, a total of 267 genes were identified that were significantly up- or downregulated in PBMCs of WT-NOD2 patients, compared to healthy donors after challenge with vitamin D and/or a combination of LPS and PGN (P < 0.05; threshold: ≥ 2-fold change). For further analysis by real-time PCR, genes with known impact on inflammation and immunity were selected that fulfilled predefined expression criteria. In a larger cohort of patients and controls, a disease-associated expression pattern, with higher transcript levels in vitamin D-treated PBMCs from patients, was observed for three of these genes, CLEC5A (P < 0.030), lysozyme (LYZ; P < 0.047) and TREM1 (P < 0.023). Six genes were found to be expressed in a NOD2-dependent manner (CD101, P < 0.002; CLEC5A, P < 0.020; CXCL5, P < 0.009; IL-24, P < 0.044; ITGB2, P < 0.041; LYZ, P < 0.042). Interestingly, the highest transcript levels were observed in patients with heterozygous NOD2 mutations.ConclusionOur data identify CLEC5A and LYZ as CD- and NOD2-associated genes of PBMCs and encourage further studies on their pathomechanistic roles.

Dataset Information

Peripheral blood methylation profiling of female Crohn's disease patients.

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Peripheral blood methylation profiling of female Crohn's disease patients.

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