Smoking-induced expression of the GPR15 gene indicates its potential role in chronic inflammatory pathologies.
Despite the described clear epigenetic effects of smoking, the effect of smoking on genome-wide gene expression in the blood is obscure. We therefore studied the smoking-induced changes in the gene-expression profile of the peripheral blood. RNA was extracted from the whole blood of 48 individuals with a detailed smoking history (24 never-smokers, 16 smokers, and 8 ex-smokers). Gene-expression profiles were evaluated with RNA sequencing, and results were analyzed separately in 24 men and 24 women. In the male smokers, 13 genes were statistically significantly (false-discovery rate <0.1) differentially expressed; in female smokers, 5 genes. Although most of the differentially expressed genes were different between the male and female smokers, the G-protein-coupled receptor 15 gene (GPR15) was differentially expressed in both male and female smokers compared with never-smokers. Analysis of GPR15 methylation identified significantly greater hypomethylation in smokers compared with that in never-smokers. GPR15 is the chemoattractant receptor that regulates T-cell migration and immunity. Up-regulation of GPR15 could explain to some extent the health hazards of smoking with regard to chronic inflammatory diseases.
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Gea
G
Kõks
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Department of Genetics, Tartu University Hospital, Tartu, Estonia.
Mari-Liis
ML
Uudelepp
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Maia
M
Limbach
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Pärt
P
Peterson
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Department of Reproductive Biology, Estonian University of Life Sciences, Tartu, Estonia.
Ene
E
Reimann
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Department of Reproductive Biology, Estonian University of Life Sciences, Tartu, Estonia. Electronic address: sulev.koks@ut.ee.
Sulev
S
Kõks
D000328:Adult; D000368:Aged; D002465:Cell Movement; D002908:Chronic Disease; D019295:Computational Biology; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044042:Receptors, Formyl Peptide / Q000187:drug effects / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics*; D018000:Receptors, Peptide / Q000187:drug effects / Q000235:genetics*; D017423:Sequence Analysis, RNA; D012907:Smoking / Q000009:adverse effects*; D015854:Up-Regulation
C103539:GPR15 protein, human; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide