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    An introduction to EpiPol (Epigenetic affecting Polymorphism) concept with an in silico identification of CpG-affecting SNPs in the upstream regulatory sequences of human AHR gene
    (Elsevier, 2020) Aftabi, Younes; Khoshkam, Zahra; Amiri-Sadeghan, Amir; Khalili, Yeganeh; Ichihara, Gaku
    DNA methylation, histone modification, and ncRNA function are the main epigenetic mechanisms involved in the regulation of gene expression and there are single nucleotide polymorphisms (SNPs) that may affect them. Although these SNPs have an important role in connecting genetic and epigenetic levels of gene regulation, they have not been classified in an independent category until now. Therefore, we introduce the EpiPol concept, which abbreviates the epigenetic affecting polymorphism and describes those variations in the regulatory se-quences of a gene, which may affect epigenetic regulations of its expression. Aryl hydrocarbon receptor (AHR) is a multifunctional regulator in cell physiology and xenobiotics metabolism and its altered regulation have been shown to result in adverse developmental and physiological outcomes. Recently, the therapeutic potential of modulating the methylation status of the AHR promoter has been discussed. Using Bioinformatics approaches, we aimed to identify the polymorphisms in upstream regulatory sequences of AHR, which may affect the epigenetic regulation of it through the introduction or removal of CpG dinucleotides that act as possible targets for DNA methylation. The 3000 bp upstream regulatory sequences of AHR, -2700 to +300 relative to the ATG codon, were obtained from NCBI. The CpG-island identified and all 105 SNPs located in it were retrieved from dbSNP. After that, 45 SNPs that cause the introduction or removal of CpGs were identified as candidate EpiPols of AHR. Then, the methylation status of these EpiPols analyzed using Bioinformatics servers, and finally, 13 SNPs were reported as predicted methylation-affecting EpiPols of the human AHR gene.
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    Investigating possible effects of aryl hydrocarbon receptor G1661A polymorphism on asthma severity in adults
    (Natl Inst Science Communication-Niscair, 2022) Aftabi, Younes; Amiri-Sadeghan, Amir; Gilani, Neda; Bakhtiyari, Nasim; Ansarin, Atefeh; Sharifi, Akbar; Ansarin, Khalil
    Aryl hydrocarbon Receptor (AhR) is a ligand-activated transcription factor with an important role in lung health. The association of AhR polymorphisms with asthma severity has not been yet investigated. We analyzed the association of G1661A, the most prevalent polymorphism of AhR, with the asthma stages in a population-based study including 555 asthmatics (Intermittent: 93, Mild: 240, Moderate: 158, and Severe: 64). The SNP was genotyped using allele-specific PCR. Obtained data were analyzed using the Generalized-Ordered Logit Estimates. Genotypes GA (OR: 0.53, CI: 0.32-0.90, P=0.019) and AA (OR: 0.22, CI: 0.06-0.76, P=0.017) were associated with decreased risk of Severe, Moderate, Mild vs. Intenaittent stage; and Severe, Moderate, vs. Mild, Intermittent stages respectively. However, Genotype GA (OR: 1.90, CI: 1.05-3.44, P=0.033), dominant model GA+AA (OR: 2.04, CI: 1.17-3.57, P=0.012), and allele A (OR: 1.68, CI: 1.06-2.66, P=0.027) were associated with increased risk of Severe stage vs. Moderate, Mild, Intermittent stages. Also, male sex and higher age were associated with an increased odds ratio for severe asthma. Furthermore, significant associations with asthma stages were found for the interactions of the SNP and sex, smoking, and alcohol consumption. In conclusion, we revealed that the mutant allele of AhR-G1661A may interact with independent variables and act as a protective factor against lower stages of asthma but it may increase the risk of severe asthma.