lunes, 3 de noviembre de 2014

Prenatal Exposure to Maternal Cigarette Smoking and DNA Methylation... - PubMed - NCBI

Prenatal Exposure to Maternal Cigarette Smoking and DNA Methylation... - PubMed - NCBI



 2014 Oct 17. [Epub ahead of print]

Prenatal Exposure to Maternal Cigarette Smoking and DNA Methylation: Epigenome-Wide Association in a Discovery Sample of Adolescents and Replication in an Independent Cohort at Birth through 17 Years of Age.

Abstract

BACKGROUND:

Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth.

OBJECTIVE:

We examined whether such alterations are present from birth through adolescence.

METHODS:

We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n=132) and at birth, during childhood, and during adolescence in a replication cohort (n=447).

RESULTS:

In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p=3.3x10-11) and CNTNAP2 (cg25949550, p=4.0x10-9) to be differentially methylated between exposed and non-exposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2were associated, respectively, with higher and lower DNAm in exposed vs. non-exposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time-points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS-significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1AHRR and GFI1 observed in that study was also evident in our discovery cohort.

CONCLUSIONS:

Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years - at least until adolescence.

PMID:
 
25325234
 
[PubMed - as supplied by publisher] 
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