Differential DNA methylation profiles of infants exposed to maternal asthma during pregnancy. Issue 9 (25th October 2013)

• Record Type: Journal Article
• Authors: Gunawardhana, Lakshitha P.; Baines, Katherine J.; Mattes, Joerg; Murphy, Vanessa E.; Simpson, Jodie L.; Gibson, Peter G.
• Is Part Of: Pediatric pulmonology. Volume 49:Issue 9(2014:Sep.)
• Page Start: 852
• Page End: 862
• Publication Date: 2013-10-25
• Subjects: Pediatric respiratory diseases -- Periodicals; Pediatrics -- Periodicals; 618.922
• DOI: 10.1002/ppul.22930
• Languages: English
• ISSNs: 8755-6863

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Summary</title> <sec id="ppul22930-sec-0001" sec-type="section"> <title>Background</title> <p>Asthma is a complex disease that involves both genetic factors and environmental exposures. Aberrant epigenetic modifications, such as DNA methylation, may be important in asthma development. Fetal exposure to maternal asthma during critical periods of in utero development may lead to epigenetic alterations that predispose infants to a greater risk of developing asthma themselves. We investigated alterations in the DNA methylation profile of peripheral blood from infants exposed to maternal asthma during pregnancy.</p> </sec> <sec id="ppul22930-sec-0002" sec-type="section"> <title>Methods</title> <p>Peripheral blood was collected from 12‐month‐old infants born to women with (n = 25) and without (n = 15) doctor diagnosed asthma during pregnancy. Genomic DNA was extracted, bisulfite converted, and hybridized to Infinium Methylation 27 arrays (Illumina), containing over27, 000 CpGs from 14, 495 genes. CpG loci in only autosomal genes were classified as differentially methylated at the 99% level (<italic>P</italic> < 0.01, |DiffScore| > 22 and delta beta >0.06).</p> </sec> <sec id="ppul22930-sec-0003" sec-type="section"> <title>Results</title> <p>There were 70 CpG loci, corresponding to 67 genes that were significantly differentially methylated. Twelve CpG loci (11 genes) showed greater than 10% comparative difference in DNA methylation, including hyper‐methylated loci of <italic>FAM181A</italic>, <italic>MRI1</italic>, <italic>PIWIL1</italic>, <italic>CHFR</italic>, <italic>DEFA1</italic>, <italic>MRPL28</italic>, <italic>AURKA</italic>, and hypo‐methylated loci of <italic>NALP1L5</italic>, <italic>MAP8KIP3</italic>, <italic>ACAT2</italic>, and <italic>PM20D1</italic> in maternal asthma. Methylation of <italic>MAPK8IP3</italic> was significantly negatively correlated with maternal blood eosinophils (r = −0.38; <italic>P</italic> = 0.022), maternal eNO (r = −0.44; <italic>P</italic> = 0.005), and maternal serum total IgE (r = −0.39, <italic>P</italic> = 0.015). Methylation of <italic>AURKA</italic> negatively correlated with maternal hemoglobin (r = −0.43; <italic>P</italic> = 0.008), infants height (r = −0.51; <italic>P</italic> < 0.001) and weight (r = −0.36; <italic>P</italic> = 0.021). Methylation of <italic>PM20D1</italic> was lower in infants born to mothers with asthma on inhaled corticosteroid treatment. Methylation of <italic>PM20D1</italic> was lower and <italic>MRI1</italic> was higher in infants born to atopic mothers without asthma.</p> </sec> <sec id="ppul22930-sec-0004" sec-type="section"> <title>Conclusions</title> <p>In an Australian study population, exposure to maternal asthma during pregnancy is associated with differential methylation profiles of infants' peripheral blood DNA, which may act as risk factors for future asthma development. <bold>Pediatr Pulmonol. 2014; 49:852–862.</bold> © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>