Causal relationships of familial hypercholesterolemia with the risk of multiple vitamin deficiencies: a Mendelian randomization study.

Background: The causal relationship between familial hypercholesterolemia (FH) and various vitamin deficiencies has not yet been elucidated. Therefore, this study investigated the cause-and-effect relationship between FH and the risk of multiple vitamin deficiencies in humans.
Methods: Mendelian randomization (MR) analysis was performed by extracting six datasets for FH, FH with ischemic heart disease (IHD), and vitamin deficiency (vitamin A, thiamine, other B-group vitamins, and vitamin D) from the FinnGen study, covering a total of 329,115; 316,290; 354,932; 354,949; 355,411 and 355,238 individuals, respectively.
Results: FH was suggestively associated with higher odds of thiamine deficiency [inverse variance weighted odds ratio (OR _IVW ) 95% confidence interval (CI): 1.62 (1.03, 2.55), P = 0.036] and vitamin D deficiencies [OR _IVW CI: 1.35 (1.04, 1.75), P = 0.024], low-density lipoprotein receptor ( LDLR ) rs112898275 variant, rs11591147 and rs499883 in proprotein convertase subtilisin/kexin 9 ( PCSK9 ), rs9644862 in cyclin-dependent kinase inhibitor 2 B antisense RNA1 ( CDKN2B-AS1 ), and rs142834163 in dedicator of cytokinesis 6 ( DOCK6 ) and rs115478735 in ABO blood group ( ABO ) strongly influenced the risk of thiamine deficiency, while the rs7412 variant in apolipoprotein E ( APOE ) mostly influenced the risk of vitamin D deficiency. FH with IHD was suggestively associated with higher odds of vitamin D deficiency (OR _IVW, weighted median [WM][95%CI]: 1.31 [1.05, 1.64]; 1.47 [1.10, 1.97]) ( P = 0.018; 0.010) without any single significant SNPs observed.
Conclusion: FH was positively associated with increased risks of thiamine and vitamin D deficiencies, revealing a prospective and unfortunate complication of FH.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Zhang, Wei, Zhou and Liu.)