DNA methylation in the Neuropeptide S Receptor 1 (NPSR1) promoter in relation to asthma and environmental factors.
Asthma and allergy are complex disorders influenced by both inheritance and environment, a relationship that might be further clarified by epigenetics. Neuropeptide S Receptor 1 (NPSR1) has been associated with asthma and allergy and a study suggested modulation of the genetic risk by environmental factors. We aimed to study DNA methylation in the promoter region of NPSR1 in relation to asthma and environmental exposures. Electrophoretic Mobility Shift Assay (EMSA) was used to investigate potential functional roles of both genotypes and methylation status in the NPSR1 promoter. DNA methylation was analysed using EpiTYPER in blood samples from two well-characterized cohorts; the BIOAIR study of severe asthma in adults and the Swedish birth cohort BAMSE. We observed that DNA methylation and genetic variants in the promoter influenced the binding of nuclear proteins to DNA, suggesting functional relevance. Significant, although small, differences in methylation were related to both adult severe asthma (p = 0.0001) and childhood allergic asthma (p = 0.01). Furthermore, DNA methylation was associated with exposures such as current smoking in adults for two CpG sites (p = 0.005 and 0.04), parental smoking during infancy in the children (p = 0.02) and in which month the sample was taken (p = 0.01). In summary, DNA methylation levels in the promoter of NPSR1 showed small but significant associations with asthma, both in adults and in children, and to related traits such as allergy and certain environmental exposures. Both genetic variation and the methylated state of CpG sites seem to have an effect on the binding of nuclear proteins in the regulatory region of NPSR1 suggesting complex regulation of this gene in asthma and allergy.
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Lovisa E
LE
Reinius
Anna
A
Gref
Annika
A
Sääf
Nathalie
N
Acevedo
Maaike
M
Joerink
Maciej
M
Kupczyk
Mauro
M
D'Amato
Anna
A
Bergström
Erik
E
Melén
Annika
A
Scheynius
Sven-Erik
SE
Dahlén
Göran
G
Pershagen
Cilla
C
Söderhäll
Juha
J
Kere
D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D015331:Cohort Studies; D018899:CpG Islands; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D024202:Electrophoretic Mobility Shift Assay; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007223:Infant; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D012907:Smoking
C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; D004247:DNA