Abstract
COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and other HUFA is a likely determinant of net signaling to induce a healthy or runaway physiological response. AA levels are determined by a non-protein coding regulatory polymorphisms that mostly affect the expression of FADS1, located in the FADS gene cluster on chromosome 11. Major and minor haplotypes in Europeans, and a specific functional insertion-deletion (Indel), rs66698963, consistently show major differences in circulating AA (>50%) and in the balance between AA and other HUFA (47–84%) in free living humans; the indel is evolutionarily selective, probably based on diet. The pattern of fatty acid responses is fully consistent with specific genetic modulation of desaturation at the FADS1-mediated 20:3→20:4 step. Well established principles of net tissue HUFA levels indicate that the high linoleic acid and low alpha-linoleic acid in populations drive the net balance of HUFA for any individual. We predict that fast desaturators (insertion allele at rs66698963; major haplotype in Europeans) are predisposed to higher risk and pathological responses to SARS-CoV-2 could be reduced with high dose omega-3 HUFA.
【저자키워드】 COVID-19, SARS-CoV-2, arachidonic acid, Highly unsaturated fatty acids, Fads gene cluster, Rs66698963, 【초록키워드】 Inflammation, Cytokine storm, High dose, thrombosis, SARS-CoV, omega-3, Genetic, polymorphism, Population, Regulatory, Desaturation, response, death, expression, predict, Fatty acid, Haplotype, Signaling, COVID-19 symptom, Major, higher risk, modulation, tissue, coding, Europeans, thrombotic, allele, circulating, insertion, pathological response, selective, INDEL, gene cluster, chromosome 11, physiological response, Affect, well, eicosanoid, FADS1, healthy, reduced, functional, induce, fatty, unsaturated, 【제목키워드】 genetics, Variability, inflammatory condition, implication, prothrombotic, biosynthesis pathway, fatty,