Relationship between obstructive sleep apnea and human leukocyte antigen variants

BackgroundObstructive sleep apnea (OSA) is a highly prevalent, complex respiratory disorder characterized by repetitive episodes of upper airway collapse. While its pathogenesis involves various anatomical and neuromuscular factors, the underlying genetic architecture remains partially elucidated. The human leukocyte antigen (HLA) system, located on chromosome 6p21, is the most polymorphic region of the human genome and plays a pivotal role in immune regulation and inflammatory pathways, which are often implicated in OSA. Historically, HLA studies in OSA relied on lower-resolution serological methods, often yielding inconsistent results. Recent advancements in targeted Next-Generation Sequencing (NGS) now provide an unprecedented opportunity to analyze HLA alleles at the four-to-six-digit level, offering the precision required to identify specific genetic markers. AimsThe primary objective of this study was to conduct a high-resolution analysis of genetic variants at the HLA-A, -B, -C, -DQB1, and -DRB1 loci using targeted NGS technology to identify predisposing or protective alleles in Turkish patients with OSA compared to a healthy cohort.Study DesignA prospective case-control study. MethodsThe study included 100 participants, consisting of 50 newly diagnosed patients with OSA and 50 healthy controls. The diagnosis of OSA was confirmed via comprehensive overnight polysomnography, and patients were categorized based on an apnea-hypopnea index of five or more events per hour. Control subjects were prospectively selected from volunteers with a low clinical risk for OSA and normal sleep patterns. High-resolution genotyping of the major HLA loci was performed using an Illumina-based targeted NGS platform. Statistical analyses were conducted to compare allele frequencies and identify significant associations between specific HLA variants and disease susceptibility. ResultsHigh-resolution NGS analysis revealed significant associations for several HLA alleles. HLA-A*02:01, HLA-C*03:03:01, HLA-C*14:03, and HLA-DRB1*04:05 alleles were found to be significantly more frequent in the OSA group compared to the control group (p=0.036, p=0.007, p=0.043, and p=0.013, respectively), suggesting a potential predisposing role. Conversely, the frequencies of HLA-A*03:01 (p=0.024) and HLA-B*35:02 (p=0.043) were significantly higher in the control cohort, suggesting that these alleles might confer a protective effect against the development of OSA. ConclusionOur findings suggest that HLA-A*02:01, HLA-C*03:03:01, HLA-C*14:03, and HLA-DRB1*04:05 alleles may serve as predisposing genetic markers for OSA in the Turkish population. The utilization of high-resolution NGS provides a more definitive genetic profile than previous methodologies. These findings contribute to the growing body of evidence regarding the immunogenetic basis of OSA and may facilitate the identification of high-risk individuals through genetic screening in the future.