SAT-636 Impact Of Mthfr C677t And A1298c Polymorphisms On Serotonin, St-2, And Homocysteine Levels In Post-covid Patients With Type 2 Diabetes Mellitus

Abstract Disclosure: K. Komisarenko: None. Background: T2DM is a multifactorial metabolic disease with significant genetic contributions. Polymorphisms in folate metabolism genes, particularly MTHFR C677T and A1298C, are associated with impaired homocysteine clearance, endothelial dysfunction, and neurotransmitter imbalance. Post-COVID metabolic stress may amplify these effects, especially in individuals with T2DM, but the combined influence of clinical and genetic factors remains poorly defined. Objective: To evaluate the association of MTHFR C677T and A1298C polymorphisms with plasma levels of serotonin, ST-2, and homocysteine in post-COVID T2DM and to develop multivariate regression models for predicting biomarker variations based on genetic and clinical profiles. Methods: This study included 250 adults with previously diagnosed T2DM who had recovered from confirmed SARS-CoV-2 infection. Demographic and clinical data, including BMI, hypertension status, and COVID-19 treatment modalities, were collected. MTHFR genotyping was performed using PCR-RFLP. Plasma levels of homocysteine were quantified via LC-MS/MS, while serotonin and ST-2 were measured using ELISA. Predictive models were constructed through multiple linear regression. Statistical significance was set at p < 0.05. Results: Patients carrying the 677T or 1298C alleles had significantly higher homocysteine (+3 µmol/L; p < 0.01) and lower serotonin levels (p < 0.05) than wild-type individuals. Elevated BMI and hypertension were additional predictors of unfavorable biomarker changes. Age was negatively associated with ST-2 levels, while a history of pulmonary insufficiency predicted increased ST-2 (p < 0.05). Dexamethasone treatment during COVID-19 was linked to increased serotonin, and oxygen therapy to reduced ST-2. All models were statistically significant (ANOVA p < 0.001) with strong explanatory power (R² = 0.87-0.91). Conclusions:MTHFR gene variants, in conjunction with clinical variables such as BMI and hypertension, influence key biochemical markers in post-COVID T2DM. Integrating genetic and metabolic profiling may inform individualized strategies for folate supplementation and cardiometabolic control. These findings support the practical implementation of genetic screening and biomarker monitoring in post-COVID endocrine care to reduce vascular, neuropsychiatric, and inflammatory complications in high-risk diabetic patients. Presentation: Saturday, July 12, 2025