National Drug Clinical Trial Center, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Front Endocrinol (Lausanne). 2024 Oct 22;15:1401260. doi: 10.3389/fendo.2024.1401260. eCollection 2024.
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.
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.
FH was suggestively associated with higher odds of thiamine deficiency [inverse variance weighted odds ratio (OR) 95% confidence interval (CI): 1.62 (1.03, 2.55), = 0.036] and vitamin D deficiencies [OR CI: 1.35 (1.04, 1.75), = 0.024], low-density lipoprotein receptor () rs112898275 variant, rs11591147 and rs499883 in proprotein convertase subtilisin/kexin 9 (), rs9644862 in cyclin-dependent kinase inhibitor 2 B antisense RNA1 (), and rs142834163 in dedicator of cytokinesis 6 () and rs115478735 in ABO blood group () strongly influenced the risk of thiamine deficiency, while the rs7412 variant in apolipoprotein E () mostly influenced the risk of vitamin D deficiency. FH with IHD was suggestively associated with higher odds of vitamin D deficiency (OR weighted median [WM][95%CI]: 1.31 [1.05, 1.64]; 1.47 [1.10, 1.97]) ( = 0.018; 0.010) without any single significant SNPs observed.
FH was positively associated with increased risks of thiamine and vitamin D deficiencies, revealing a prospective and unfortunate complication of FH.
家族性高胆固醇血症（FH）与各种维生素缺乏之间的因果关系尚未阐明。因此，本研究调查了 FH 与人类多种维生素缺乏症风险之间的因果关系。
从 FinnGen 研究中提取了 6 个 FH、FH 伴缺血性心脏病（IHD）和维生素缺乏症（维生素 A、硫胺素、其他 B 族维生素和维生素 D）的数据集，共涵盖 329115、316290、354932、354949、355411 和 3554238 人。
FH 与硫胺素缺乏症的发病风险升高相关（逆方差加权比值比（OR）95%置信区间（CI）：1.62（1.03，2.55）， = 0.036）和维生素 D 缺乏症（OR CI：1.35（1.04，1.75）， = 0.024），低密度脂蛋白受体（）rs112898275 变异体、前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（）rs11591147 和 rs499883、细胞周期蛋白依赖性激酶抑制剂 2B 反义 RNA1（）rs9644862、细胞分裂蛋白 6（）rs142834163 和 ABO 血型（）rs115478735 强烈影响硫胺素缺乏症的发病风险，而载脂蛋白 E（）rs7412 变异体主要影响维生素 D 缺乏症的发病风险。FH 伴 IHD 与维生素 D 缺乏症的发病风险升高相关（加权中位数 [WM] [95%CI]：1.31 [1.05，1.64]；1.47 [1.10，1.97]）（ = 0.018；0.010），但未观察到任何单一显著 SNP。
FH 与硫胺素和维生素 D 缺乏症风险增加相关，揭示了 FH 的一种潜在不幸的并发症。
