DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood.
Am J Respir Crit Care Med
; 185(9): 937-43, 2012 May 01.
Article
em En
| MEDLINE
| ID: mdl-22323304
ABSTRACT
RATIONALE Epigenetic changes may play a role in the occurrence of asthma-related phenotypes. OBJECTIVES:
To identify epigenetic marks in terms of DNA methylation of asthma-related phenotypes in childhood, and to assess the effect of prenatal exposures and genetic variation on these epigenetic marks.METHODS:
Data came from two cohorts embedded in the Infancia y Medio Ambiente (INMA) PROJECT Menorca (n = 122) and Sabadell (n = 236). Wheezing phenotypes were defined at age 4-6 years. Cytosine-guanine (CpG) dinucleotide site DNA methylation differences associated with wheezing phenotypes were screened in children of the Menorca study using the Illumina GoldenGate Panel I. Findings were validated and replicated using pyrosequencing. Information on maternal smoking and folate supplement use was obtained through questionnaires. Dichlorodiphenyldichloroethylene was measured in cord blood or maternal serum. Genotypes were extracted from genome-wide data. MEASUREMENT AND MAINRESULTS:
Screening identified lower DNA methylation at a CpG site in the arachidonate 12-lipoxygenase (ALOX12) gene in children having persistent wheezing compared with those never wheezed (P = 0.003). DNA hypomethylation at ALOX12 loci was associated with higher risk of persistent wheezing in the Menorca study (odds ratio per 1% methylation decrease, 1.13; 95% confidence interval, 0.99-1.29; P = 0.077) and in the Sabadell study (odds ratio, 1.16; 95% confidence interval, 1.03-1.37; P = 0.017). Higher levels of prenatal dichlorodiphenyldichloroethylene were associated with DNA hypomethylation of ALOX12 in the Menorca study (P = 0.033), but not in the Sabadell study (P = 0.377). ALOX12 DNA methylation was strongly determined by underlying genetic polymorphisms.CONCLUSIONS:
DNA methylation of ALOX12 may be an epigenetic biomarker for the risk of asthma-related phenotypes.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Araquidonato 12-Lipoxigenase
/
Sons Respiratórios
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Metilação de DNA
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Espanha