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

Cheng Zhang; Gang Wei; Huan Zhou; Lin Liu

doi:10.3389/fendo.2024.1401260

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

Front Endocrinol (Lausanne). 2024 Oct 22:15:1401260. doi: 10.3389/fendo.2024.1401260. eCollection 2024.

Authors

Cheng Zhang¹, Gang Wei², Huan Zhou¹, Lin Liu¹

Affiliations

¹ National Drug Clinical Trial Center, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
² Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Abstract

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.

Keywords: familial hypercholesterolemia; genetic association; human; thiamine deficiency; vitamin D deficiency.

MeSH terms

Apolipoproteins E / genetics
Avitaminosis / complications
Avitaminosis / epidemiology
Avitaminosis / genetics
Female
Humans
Hyperlipoproteinemia Type II* / blood
Hyperlipoproteinemia Type II* / complications
Hyperlipoproteinemia Type II* / epidemiology
Hyperlipoproteinemia Type II* / genetics
Male
Mendelian Randomization Analysis*
Polymorphism, Single Nucleotide
Proprotein Convertase 9 / genetics
Receptors, LDL / genetics
Risk Factors
Thiamine Deficiency / epidemiology
Thiamine Deficiency / genetics
Vitamin D Deficiency / complications
Vitamin D Deficiency / epidemiology
Vitamin D Deficiency / genetics

Substances

Proprotein Convertase 9
PCSK9 protein, human
Receptors, LDL
LDLR protein, human
Apolipoproteins E

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the National Natural Science Foundation of China (No. 82370847; 82000804, GW).