AUTHOR=Zhang Cheng , Wei Gang , Zhou Huan , Liu Lin 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1401260

DOI=10.3389/fendo.2024.1401260

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>FH was suggestively associated with higher odds of thiamine deficiency [inverse variance weighted odds ratio (OR<sub>IVW</sub>) 95% confidence interval (CI): 1.62 (1.03, 2.55), <italic>P</italic> = 0.036] and vitamin D deficiencies [OR<sub>IVW</sub> CI: 1.35 (1.04, 1.75), <italic>P</italic> = 0.024], low-density lipoprotein receptor (<italic>LDLR</italic>) rs112898275 variant, rs11591147 and rs499883 in proprotein convertase subtilisin/kexin 9 (<italic>PCSK9</italic>), rs9644862 in cyclin-dependent kinase inhibitor 2 B antisense RNA1 (<italic>CDKN2B-AS1</italic>), and rs142834163 in dedicator of cytokinesis 6 (<italic>DOCK6</italic>) and rs115478735 in ABO blood group (<italic>ABO</italic>) strongly influenced the risk of thiamine deficiency, while the rs7412 variant in apolipoprotein E (<italic>APOE</italic>) mostly influenced the risk of vitamin D deficiency. FH with IHD was suggestively associated with higher odds of vitamin D deficiency (OR<sub>IVW,</sub> weighted median [WM][95%CI]: 1.31 [1.05, 1.64]; 1.47 [1.10, 1.97]) (<italic>P</italic> = 0.018; 0.010) without any single significant SNPs observed.</p></sec><sec><title>Conclusion</title><p>FH was positively associated with increased risks of thiamine and vitamin D deficiencies, revealing a prospective and unfortunate complication of FH.</p></sec>