Health & Environmental Research Online (HERO)


Print Feedback Export to File
190167 
Journal Article 
Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma 
Perera, F; Tang, WY; Herbstam, J; Tand, D; Levin, L; Miller, R; Ho, SM 
2009 
1 
PLoS ONE
EISSN: 1932-6203 
4 
2 
e4488 
English 
19221603 
WOS:000265485700013 
In a longitudinal cohort of ~700 children in New York City, the prevalence of asthma (>25%) is among the highest in the
US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons
(PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks
associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers
completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction
fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA
sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences
were found to be homologous to known genes having one or more 5'-CpG island(s) (5'-CGI). Of these, acyl-CoA synthetase
long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5'-CGI in
UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was
therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5'-CGI was
found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m3 (OR = 13.8; p<0.001;
sensitivity = 75%; specificity = 82%) and with a parental report of asthma symptoms in children prior to age 5 (OR = 3.9;
p<0.05). Thus, if validated, methylated ACSL3 5'CGI in UCWBC DNA may be a surrogate endpoint for transplacental PAH
exposure and/or a potential biomarker for environmentally-related asthma. This exploratory report provides a new blueprint
for the discovery of epigenetic biomarkers relevant to other exposure assessments and/or investigations of exposuredisease
relationships in birth cohorts. The results support the emerging theory of early origins of later life disease
development.