Role of metabolites in mediating the effect of triacylglycerol on aplastic anemia.

ABSTRACT

BACKGROUND: Observational studies have found a link between lipid metabolism disorders and aplastic anemia (AA). However, due to confounding variables and reverse causation, it is difficult to conclude such a causal link. The precise mechanism and potential implications of lipid metabolism disorder in AA remain unclear, necessitating further studies in this area. METHOD: This study aimed to examine the causal relationship between 38 different subtypes of triacylglycerols and AA using two-sample Mendelian randomization (MR). Additionally, two-step MR analyses were conducted to investigate the mediating effects of vitamin A to oleoyl-linoleoyl-glycerol (181-182) ratio. RESULTS: MR analysis showed that triacylglycerol (533) levels were positively associated with the risk of AA [inverse variance weighting (IVW) odds ratio (OR) = 1.131,95% confidence interval (CI)1.029-1.243, P = 0.011; Bayesian weighted MR (BWMR) OR = 1.137,95% CI1.031-1.254, P = 0.010]. Triacylglycerol (533) level showed no inverse causality with AA (IVWP = 0.834; BWMRP = 0.349). Mediation analyses showed that increasing the vitamin A to oleoyl-linoleoyl-glycerol (181-182) ratio can decrease the risk of AA. CONCLUSION: This study revealed the association between vitamin A to oleoyl-linoleoyl-glycerol (181-182) ratio, triacylglycerol (533) levels and AA, and indicated that lowering triacylglycerol (533) levels can reduce the risk of AA.