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Risk factors – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Methylation of CpGs, i.e. regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases, has been observed for genes that respond to tobacco smoke toxins in offspring of smokers who smoked during pregnancy, such as AHRR and CYP1A1, that are key members of the aryl hydrocarbon receptor pathway that respond to PAHs. CpG methylation was also detected in the genes involved in fetal development in cord blood which may be a mechanism by which maternal smoke exposure (MSE) impacts fetal growth.
The interplay between aryl hydrocarbon receptor, H. pylori, tryptophan, and arginine in the pathogenesis of gastric cancer
Published in International Reviews of Immunology, 2022
Marzieh Pirzadeh, Nastaran Khalili, Nima Rezaei
The AHR is a ligand-activated transcription factor which belongs to the xenobiotic type receptor family that governs the expression of various set of genes such as cytochrome P450 1A1 (CYP1A1), cytochrome P450 1B1 (CYP1A2), and growth regulatory proteins [7]. AHR also plays a major role in cell homeostasis, covering diverse physiological aspects such as cell proliferation, differentiation, motility, and migration [7]. Moreover, many studies have shown the role of AHR in promoting and modulating antibacterial response [8]. It has been shown that constitutively active AHR expression in transgenic mice reduces their life survival and induces tumor formation in the glandular part of the stomach [9]. The observed oncogenic potential of this receptor might possibly be justified by its role in the regulation of cell proliferation [10]. On the other hand, further studies have introduced AHR as a probable therapeutic target for the treatment of gastric cancer due to its contribution to cell cycle arrest [11,12]. A recent study showed that AHR and aryl hydrocarbon receptor repressor (AHRR) expression were reduced in positive H. pylori tissue, and this reduction enhanced tumor necrosis factor-α (TNF-α), IL-8, and IL-1β secretion [6].
Plasma levels of polychlorinated biphenyl, genetic polymorphisms, and the risk of advanced stage endometriosis
Published in Gynecological Endocrinology, 2020
Miran Kim, Sung Hoon Kim, Hyun Jin Kim, Dong Hee Whang, Sung-Cheol Yun, Sa Ra Lee, Hee Dong Chae, Byung Moon Kang
Glutathione-S-transferase (GST) is responsible for metabolism of xenobiotics and loss of aryl hydrocarbon receptor repressor (AhRR) function can lead to increased susceptibility to toxic effects of dioxin-like compounds or PCBs. We previously showed that the AhRR codon 185 and GSTT1 polymorphisms are associated with the risk of advanced stage endometriosis, which suggests a possible role of genes involved in xenobiotic detoxification process in the pathogenesis of endometriosis [6]. In the present study we analyzed the plasma levels of several congeners of PCBs along with the genetic polymorphisms of GSTM1/T1, and AhRR codon 185 in women with and without advanced stage endometriosis, and investigated whether the risk of endometriosis could be affected not only by the plasma levels of PCBs but also by the polymorphisms of genes involved in detoxification pathways.
Global methylation profiles in buccal cells of long-term smokers and moist snuff consumers
Published in Biomarkers, 2018
Walter J. Jessen, Michael F. Borgerding, G. L. Prasad
The AHRR gene has been shown to be differentially methylated in previous studies of smokers (Joubert et al. 2012, Monick et al. 2012, Philibert et al. 2012, Shenker et al. 2013, Besingi and Johansson 2014, Joehanes et al. 2016). The most significant site in our study (cg05575921) was also the most significant in previous studies (Joubert et al. 2012, Sun et al. 2013, Zeilinger et al. 2013, Besingi and Johansson 2014, Joehanes et al. 2016). AHRR is a negative regulator of the aryl hydrocarbon receptor (AHR) gene that codes for a protein that binds to a wide range of xenobiotics. AHR induces the expression of CYP1A1 and other genes involved in the metabolism of xenobiotics such as dioxin and polycyclic aromatic hydrocarbons (PAHs), as well as nicotine. AHRR has been proposed to be a tumour suppressor gene in multiple types of human cancers (Zudaire et al. 2008). Optimal functioning of the xenobiotic detoxification system requires retinoids for sensing, detoxifying, and eliminating xenobiotics (Shmarakov 2015), and we find that response to the retinoid vitamin A is impacted in the CTR signature.