Skip to main content

ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Systems Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1401260

Causal Relationships of Familial Hypercholesterolemia with the Risk of Multiple Vitamin Deficiencies: A Mendelian Randomization Study

Provisionally accepted
Cheng Zhang Cheng Zhang 1Gang Wei Gang Wei 2Lin Liu Lin Liu 3*
  • 1 Room 603, No.6, Lane 477, Gaojing Road, Baoshan District, Shanghai, China
  • 2 Beijing Tongren Hospital, Capital Medical University, Beijing, Beijing Municipality, China
  • 3 National Drug Clinical Trial Institute, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China

The final, formatted version of the article will be published soon.

    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 (ORIVW) 95% confidence interval (CI): 1.62 (1.03, 2.55), P = 0.036] and vitamin D deficiencies [ORIVW 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 (ORIVW, 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.

    Keywords: Familial Hypercholesterolemia, Genetic association, human, Thiamine Deficiency, Vitamin D Deficiency

    Received: 03 Apr 2024; Accepted: 02 Oct 2024.

    Copyright: © 2024 Zhang, Wei and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lin Liu, National Drug Clinical Trial Institute, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.