The relationship of obstructive sleep apnea syndrome (OSAS) phenotypes with TNF-alfa (-308G/A), PGE2 receptor polymorphism

Obstructive sleep apnea (OSAS) is a disease characterized by recurrent obstruction of the upper airways during sleep, increased respiratory effort against obstruction, decreased oxygen saturation, and sleep disruptions. Today, the diagnosis of OSAS is made with PSG. For the diagnosis of OSAS, AHI ≥ 5/h should be determined; Treatment is planned by classifying mild, moderate and severe OSAS according to AHI being 5-15, 16-30 and >30/hr. The use of AHI in the diagnosis and determination of the severity of OSAS, which is a clinically heterogeneous disease, is insufficient to better understand the genetic and biological basis of the disease. Therefore, in order to understand the genetic biological basis and pathogenesis of OSAS, it is necessary to classify patients as phenotypes. Hypoxia-reoxygenation that develops during recurrent episodes of apnea and hypopnea in OSAS causes local and systemic inflammation by generating reactive oxygen radicals and causing oxidative stress. Tumor necrosis factor alpha (TNF-alpha), which has an important role in inflammation, plays a role in the regulation of pro-inflammatory cytokines during sleep. The TNF-alpha 308G/A polymorphism in OSAS has been associated with increased TNF-alpha levels implicated in intermittent hypoxemia. In addition, the rs1409986 SNP polymorphism in the PGE2 receptor (PTGER3), which is involved in inflammation, was found to be significantly associated with OSAS. In this study, we aimed to clinically classify OSAS patients newly diagnosed in our clinic between 2020-2022, to examine their relationship with OSAS phenotypes by looking at TNF-alpha (-308G/A), PGE2 receptor polymorphism in these patients, to gain information that will contribute to the etiology of OSAS, and to introduce new information in terms of treatment. It is intended to guide the methods. That's why at PSG. 100 studies with AHI ≥ 5 diagnosed with OSAS were included and were divided into phenotypes according to symptoms, demographic characteristics, comorbidities, and PSG findings. Patients with AHI <5 were evaluated as simple snoring and constituted the control group. For genetic evaluation, TNF-alpha (-308G/A), PGE2 rs1409986 SNP polymorphisms were studied from blood samples taken from the study and control groups. The phenotypic groups formed in our study; It consisted of 72 (%72) patients in Cluster 1, 12 (%12) in Cluster 2, and 16 (%16) patients in Cluster 3. Of Cluster 1, %31,9 consisted of individuals with AHI between 5-15, %31,9 with AHI between 16-30, and %36.1 with AHI ≥30. Cluster 2 consisted of %16,7 individuals with AHI between 16-30 and %83,3 with AHI ≥30, while cluster 3 consisted of individuals with %100 AHI ≥30 and it was statistically significant between groups. determined (p=0,0001). Considering the AHI classification and mean AHI values, the phenotypic group with the most severe disease clinic in our study was evaluated as Cluster 3, followed by Cluster 2 and Cluster 1 (Cluster 1; 24,56, Cluster 2; 39,74, Cluster 3; 80,48, p:0,0001). Similarly, while the mean number of obstructive apnea was found to be lowest in Cluster 1 (94,53/hour), it was higher in Cluster 2 (154,75/hour) and Cluster 3 (340,31/hour) (p:0,001). The mean oxygen saturation was found to be %92,45 in Cluster 1,% 86,17 in Cluster 2, and %87,94 in Cluster 3, which supports other findings (p:0,001). Although all individuals with AHI values between 5-15 were in Cluster 1, %92 of individuals with AHI values between 16-30 were in Cluster 1 and %8 were in Cluster 2; Of those with AHI ≥30, %50 were in Cluster 1, %19,2 in Cluster 2, and %30,7 in Cluster 3. This shows that AHI values may differ within OSAS phenotypic clusters and should not be considered as the only parameter in classifying the disease. In our study, when the TNF-α(-308G/A) polymorphism and PGE2 receptor polymorphism of the control group consisting of healthy individuals and patients diagnosed with OSAS were compared, both polymorphisms were observed more frequently in the OSAS group and statistically significant differences were found as stated in the literature (respectively; p=0,011, p= 0,014). When the frequency of detection of TNF-α(-308G/A) polymorphism according to clusters was evaluated, it was found in %75 of individuals in Cluster 3,% 55,6 in Cluster 1, and %33,3 in Cluster 2. Although there was no statistically significant difference between clusters (p=0,088), the frequency of TNF-α(-308G/A) polymorphism was found to be higher in Cluster 3, which is the most severe disease group according to PSG data, than in other groups. PGE2 receptor polymorphism detection rates were similar in all clusters, and no statistically significant difference was found (p=0,962). In conclusion, our findings are clinically important in two main aspects. Firstly; to classify them into more homogeneous classes called 'Phenotypes', including AHI values, based on clinical, pathophysiological, cellular, biological and molecular features; Second, identifying the different clinical profiles of OSAS provides a basis for offering more personalized treatments in the future. Further research is needed to explore the mechanisms underlying different clinical phenotypes, including genotypic differences associated with different clinical presentations.