Nasal Cell DNA Methylation, Inflammation, Lung Function and Wheezing in Children with Asthma

Abstract

Aims: DNA methylation is increasingly proposed as a mechanism for underlying asthma-related inflammation. However, epigenetic studies are constrained by uncertainties on whether samples that can be easily collected in human individuals can provide informative results. Methods: Two nasal cell DNA samples were collected on different days by nasal brushings from 35 asthmatic children aged between 8 and 11 years old. We correlated DNA methylation of IL-6, iNOS, Alu and LINE-1 with fractional exhaled nitric oxide, forced expiratory volume in 1 s and wheezing. Results: Fractional exhaled nitric oxide increased in association with lower promoter methylation of both IL-6 (+29.0%; p = 0.004) and iNOS (+41.0%; p = 0.002). Lower IL-6 methylation was nonsignificantly associated with wheezing during the week of the study (odds ratio = 2.3; p = 0.063). Conclusion: Our findings support the use of nasal cell DNA for human epigenetic studies of asthma.

KEYWORDS::

• airway obstruction
• asthma
• children
• DNA methylation
• epigenetics
• inflammation

Financial & competing interests disclosure

Funding was recieved from project ‘Environment and Health in Sicily‘ – WHO Europe, Health Impact Assessment, Methods and Strategies, Rome Office and Regione Siciliana; PRIN20072S2HT8 Grant – Italian Ministry of Education and Scientific Research; ESTHER2007-5469 Grant – non-profit CARIPLO Foundation; and HSPH–NIEHS Center for Environmental Health New Investigator Fund (P30ES000002). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

Funding was recieved from project ‘Environment and Health in Sicily‘ – WHO Europe, Health Impact Assessment, Methods and Strategies, Rome Office and Regione Siciliana; PRIN20072S2HT8 Grant – Italian Ministry of Education and Scientific Research; ESTHER2007-5469 Grant – non-profit CARIPLO Foundation; and HSPH–NIEHS Center for Environmental Health New Investigator Fund (P30ES000002). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.