Decreased Aryl Hydrocarbon Receptor Gene Expression and Polymorphic Variants Association with Increase COPD Risk

Maryam Sadr,1 Alireza Asgari,2 Sara Assadiasl,1 Hanieh Mojtahedi,1 Alireza Abdollahi,3 Mohammad Hossein Nicknam,1 Maryam Edalatifard,2 Narjes Soleimanifar1 1Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran; 2Thoracic Research Center, Tehran University of Medical Sciences, Imam Khomeini Hospital, Tehran, Iran; 3Department of Pathology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Narjes Soleimanifar, Email [email protected] Maryam Edalatifard, Email [email protected]: The Aryl Hydrocarbon Receptor (AHR) is a ligand-activated transcription factor that regulates gene expression, including those involved in metabolizing xenobiotic chemicals. The association of AHR with the onset and severity of Chronic Obstructive Pulmonary Disease (COPD) has not yet been elucidated. This study aimed to investigate the correlation between two AHR polymorphisms and the expression levels of this gene in COPD patients compared to healthy controls.Methods: The AHR gene expression level and frequency of two polymorphisms, rs2066853 and rs2074113, were studied in 154 COPD patients and 145 healthy individuals using RT-PCR and AS-PCR methods respectively.Results: The findings showed a significant difference in the frequencies of G and A, as well as GG and GA genotypes in rs2066853 between patients and healthy controls [G: OR: 0.4, CI: 0.24– 0.67, (p=0.0002); A: OR: 2.44, CI: 1.48– 4.03, (p=0.0002); genotypes GG: OR: 0.37, CI: 0.21– 0.65, (p=0.0002) and GA: OR: 2.42, CI: 1.40– 4.18 (p=0.001)]. Additionally, the GT genotype frequency in the rs2074113 was different between two groups [GT: OR: 0.23, CI: 0.07– 0.72, (p=0.008)]. Moreover, AHR gene expression was significantly lower in COPD patients compared to healthy controls (P=0.03). Noteworthy, individuals with the GA genotype in rs2066853 exhibited lower AHR expression levels than those with the GG genotype.Conclusion: The presence of allele A and the GA genotype of the rs2066853 polymorphism in the AHR gene is significantly associated with COPD, suggesting a genetic predisposition. Moreover, reduced AHR expression in patients supports its key role in COPD pathogenesis.Keywords: chronic obstructive pulmonary disease, aryl hydrocarbon receptor, single nucleotide polymorphism, gene expression