Smoking-induced expression of the GPR15 gene indicates its potential role in chronic inflammatory pathologies

The American Journal of Pathology
Gea KõksSulev Kõks

Abstract

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.

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Citations

Mar 10, 2016·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Ronald AndersonMohammed Tikly
Dec 22, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Xu GaoHermann Brenner
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Dec 15, 2020·Journal of Psychosomatic Research·Allan M AndersenRobert A Philibert
Dec 13, 2016·Pediatrics·Catherine MetayerMark Miller

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