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PMID: 23546690 Published · ppublish English Case Reports Journal Article Multicenter Study Research Support, Non-U.S. Gov't

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

Human genetics ·Vol. 132 ·No. 7 ·2013-07-00 ·Pages 811-22

Naumova AK, Al Tuwaijri A, Morin A, Vaillancourt VT, Vaillancout VT, Madore AM, Berlivet S, Kohan-Ghadr HR, Moussette S, Laprise C

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.

MeSH Terms
Adolescent Adult Aged Aged, 80 and over Aging Asthma/genetics,metabolism Child Child, Preschool Chromosomes, Human, Pair 17/genetics,metabolism DNA Methylation/genetics Egg Proteins/genetics,metabolism Female Follow-Up Studies Gene Expression Regulation/genetics Genetic Loci Humans Infant, Newborn Male Membrane Proteins/genetics,metabolism Middle Aged Sex Characteristics
Chemicals
Egg Proteins Membrane Proteins ZPBP2 protein, human
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Naumova Anna K
Department of Obstetrics and Gynecology, McGill University, Montreal, QC, H3A 1A1, Canada. anna.naoumova@mcgill.ca
Al Tuwaijri Abeer
Morin Andréanne
Vaillancourt Vanessa T
Vaillancout Vanessa T
Madore Anne-Marie
Berlivet Soizik
Kohan-Ghadr Hamid-Reza
Moussette Sanny
Laprise Catherine
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Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
1432-1203
DOI
10.1007/s00439-013-1298-z
Email
anna.naoumova@mcgill.ca
Published
2013-07-00
Epub
2013-00-02
Pages
811-22
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
Grants
Canadian Institutes of Health Research · 115117-1 · Canada
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1007/s00439-013-1298-z View journal details
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