Introduction<br />Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and poorly understood disorder characterized by severe fatigue that does not improve with rest.<br />Recent evidence suggests that genetic predisposition and epigenetic alterations may play key roles in susceptibility and symptom development.<br /><br />Genetic Basis of ME/CFS<br /> • Genome-wide association studies (GWAS) have begun to identify genetic variants related to immunity, energy metabolism, and mitochondrial function.<br /> • Candidate genes include NR3C1 (cortisol receptor), HLA genes (immune regulation), and genes involved in inflammatory pathways.<br /><br />Epigenetic Regulation<br /><br />DNA Methylation<br /> • Recent studies have shown abnormal methylation patterns in immune and inflammatory genes in ME/CFS patients.<br /> • These changes may result from chronic stress or viral infections.<br /><br />Non-coding RNAs<br /> • Specific microRNAs (miRNAs) are altered in patients and may serve as potential biomarkers for diagnosis.<br /><br />Histone Modifications<br /> • Although less studied, early findings suggest dysregulation in chromatin accessibility affecting genes involved in energy metabolism.<br /><br />Gene–Environment Interaction<br /> • ME/CFS is thought to arise from a complex interaction between genetic susceptibility and environmental exposures (such as viral infections or psychological stress).<br /> • Epigenetic changes act as the bridge explaining how environmental factors can reprogram gene expression.<br /><br />Future Applications<br /> 1. Early Diagnosis: Using DNA methylation or miRNA profiles as biomarkers.<br /> 2. Personalized Therapy: Targeting epigenetic pathways (e.g., inhibitors of DNA methylation enzymes).<br /> 3. Prevention: Monitoring genetically predisposed individuals to prevent disease development.<br /><br />Conclusion<br />ME/CFS is no longer viewed merely as a psychological disorder but rather as a condition linked to complex genetic and epigenetic mechanisms. Future research will determine whether modifying these molecular markers can lead to effective treatments.<br /><br />University of Al-Mustaqbal – the first university in Iraq<br />Department of Medical Laboratory Techniques – ranked first in the Iraqi National Classification