Abstract WP251: Dietary Methionine and Homocysteine Level Interaction and Recurrent Stroke

Abstract

Background: The folate one-carbon metabolism pathway (FOCM) provides vital one-carbon units for epigenetic regulation. Genetic variants in FOCM genes may affect methionine metabolism. Elevated circulating homocysteine (Hcy), a FOCM byproduct, is linked to increased stroke risk. However, the protective effects of dietary regulation of methionine and Hcy levels against recurrent stroke are uncertain. Objective: To investigate dietary methionine (METH) and its interaction with post-methionine load Hcy levels (POST) with recurrent stroke risk; to assess if genetically determined POST and its interaction with METH predict recurrent stroke risk. Methods: We utilized the Vitamin Intervention for Stroke Prevention (VISP) trial to estimate hazards ratios of METH and its interaction with POST on recurrent stroke with a Cox proportional hazards model. We also generated a POST polygenic risk score (PRS) with ridge regression using previously identified polymorphisms, located within ALDH1L1, CPS1, GNMT, and PSPH, as indicators of FOCM function. Results: The participants (n = 2,100; 64% men) had a mean (SD) age of 67 (11) years. Ancestry consisted of 82% European, 12% African, and 5.7% Other. A small portion of participants had missing POST values (7.3%). Clinical POST (HR 1.02; 95%CI 0.98, 1.06) and its interaction with METH (HR 0.99; 95% CI 0.97, 1.01) were not associated with recurrent stroke risk. Similarly, there was no significant relationship observed between PRS POST (HR 0.96; 95%CI 0.80, 1.15) and its interaction with METH (HR 1.02; 95% CI 0.94, 1.10). Conclusion: Dietary methionine and post-methionine load Hcy levels neither interact nor predict recurrent stroke risk. Our PRS approach showed similar negative findings. The relationship of the FOCM and recurrent stroke risk may lie in epigenetics.