Proximity effects and disease-related differences in DNA methylation among asthma patients near the Sohar Industrial Port, Oman

Abstract

Air pollution is increasingly recognized as a contributor to worsening asthma severity, possibly mediated by DNA methylation. We assessed links between air pollution, DNA methylation, and asthma severity among patients living near the Sohar Industrial Port (SIP) in Oman. In 130 asthmatics, global methylation by ELISA and promoter methylation of LINE-1, IL-6, P53, TLR2, and CDKN2Ap by MS-HRM were measured. Exposure was indexed by proximity (High <12 km; Low ≥12 km), and analyses considered severity with multiplicity control. LINE-1 and global methylation were stable across groups. IL-6 and P53 were higher in asthma than controls at the nominal level; after correction, only P53 elevation in Moderate/Severe asthma persisted within the Low-exposure zone. Proximity effects were limited, with a distance effect for CDKN2Ap in the Moderate/Severe subgroup that remained after correction, while IL-6, TLR2, and P53 showed no consistent High-Low differences. Males and older patients showed higher global methylation, with age effects persisting after adjustment. Several exposures/medications showed nominal, inconsistent associations with higher IL-6, P53, and/or global methylation; dust exposure showed no gene-specific differences. Overall, robust signals were restricted to the CDKN2Ap proximity effect and zone-specific P53 elevation in Moderate/Severe asthma. DNA methylation may be a biomarker of asthma progression; future studies will evaluate matched gene expression.

Keywords: Air pollution; DNA methylation; Oman; asthma; environmental exposures; epigenetics; respiratory diseases.