Epigenome Variation in Severe Asthma

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Abstract

Background:

Asthma is a complex heterogeneous disease process with mild, moderate, and severe classifications. Although the science of genomics has opened our understanding of the molecular underpinnings of asthma, epigenetics is emerging as a mechanism whereby the expression of disease-risk genes may be influenced by environmental exposure.

Objectives:

The purpose of this article is to discuss the methodology of data collection and evaluation involved in genome-wide methylation profiling (epigenomic) through presentation of data generated for a population presenting with severe asthma.

Method:

Over 14,000 gene promoter sites were analyzed for methylation status among six subjects with severe asthma and four normal controls in this pilot study. Two duplicate samples were used as technical replicates. Nonsmoking case/control subjects were chosen based on similar gender and age. Blood samples were used for DNA extraction, and methylation data were collected utilizing the Illumina Infinium HumanMethylation27BeadChip platform.

Results:

Technical replicates were highly concordant, and statistically significant differences were found in methylation profiles between subjects with severe asthma and normal controls (p < 10-8), some previously reported with pulmonary function and others never before reported. After correction for multiple testing, three gene promoter regions remained statistically different: FAM181A, ZNF718, and MRI1.

Discussion:

This research supports the internal validity of the Illumina platform in methylation analysis of DNA from stored blood samples. Although significant differences in methylation were noted between subjects with severe asthma and controls, the small sample size warrants further investigation into these results.

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