NDLI: Sex- and age-dependent DNA methylation at the 17q12-q21 locus associated with childhood asthma

Content Provider	Springer Nature Link
Author	Naumova, Anna K. Al Tuwaijri, Abeer Morin, Andréanne Vaillancout, Vanessa T. Madore, Anne Marie Berlivet, Soizik Kohan Ghadr, Hamid Reza Moussette, Sanny Laprise, Catherine
Copyright Year	2013
Abstract	Chromosomal region 17q12-q21 is one of the best-replicated genome-wide association study (GWAS) hits and associated with childhood-onset asthma. However, the mechanism by which the genetic association is restricted to childhood-onset disease is unclear. During childhood, more boys than girls develop asthma. Therefore, we tested the hypothesis that the 17q12-q21 genetic association was sex-specific. Indeed, a TDT test showed that in the Saguenay-Lac-Saint-Jean familial collection, the 17q12-q21 association was significant among male, but not among female asthmatic subjects. We next hypothesized that the bias in the genetic association resulted from sex-specific and/or age-dependent DNA methylation at regulatory regions and determined the methylation profiles of five 17q12-q21 gene promoters using the bisulfite sequencing methylation assay. We identified a single regulatory region within the zona pellucida binding protein 2 (ZPBP2) gene, which showed statistically significant differences between males and females with respect to DNA methylation. DNA methylation also varied with age and was higher in adult males compared to boys. We have recently identified two functionally important polymorphisms, both within the ZPBP2 gene that influence expression levels of neighboring genes. Combined with the results of the present work, these data converge pointing to the same 5 kb region within the ZPBP2 gene as a critical region for both gene expression regulation and predisposition to asthma. Our data show that sex- and age-dependent DNA methylation may act as a modifier of genetic effects and influence the results of genetic association studies.
Starting Page	811
Ending Page	822
Page Count	12
File Format	PDF
ISSN	03406717
Journal	Human Genetics
Volume Number	132
Issue Number	7
e-ISSN	14321203
Language	English
Publisher	Springer-Verlag
Publisher Date	2013-04-02
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Genetics Molecular Medicine Gene Function Metabolic Diseases
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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