维生素D相关指标与肌少症诊断参数孟德尔随机化研究

doi:10.12183/j.scjpm.2025.0984

摘要/Abstract

摘要： 目的运用孟德尔随机化（MR）方法探索维生素D相关指标与肌少症诊断参数的因果关联。方法主要分析采用TSMR方法探索维生素D相关指标（25-羟维生素D水平、维生素D结合蛋白、维生素D缺乏、维生素D补充剂）与肌少症诊断参数[低握力、四肢骨骼肌质量（ALM）、步速]的因果关联,同时采用MVMR方法探索二者的独立因果效应。随后,更换肌少症诊断参数数据进行复制分析,并对主要、复制TSMR分析结果进行Meta分析。结果主要分析、多变量和复制分析的MR结果未发现维生素D相关指标与肌少症诊断参数有显著因果关系,Meta分析结果显示,未患维生素D缺乏和步速（β=0.001,95% CI=0.000 2~0.001 8,P=0.019）、低握力（OR=0.993,95% CI=0.987~0.999,P=0.015）,25（OH）D水平和步速（β=0.015,95% CI=0.004~0.027,P=0.009）存在因果关系。结论维持最佳25（OH）D水平有助于防止步速水平的下降,而未患维生素D缺乏还可降低低握力的发生风险。

关键词: 25-羟维生素D, 肌少症, 孟德尔随机化, Meta分析

Abstract: Objective To explore the causal relationships between vitamin D-related biomarkers and diagnostic parameters of sarcopenia utilizing Mendelian Randomization (MR) approaches. Methods Two-sample Mendelian randomization (TSMR) analyses were conducted to investigate the causal associations between vitamin D-related biomarkers(including serum 25-hydroxyvitamin D levels, vitamin D binding protein, vitamin D deficiency, and vitamin D supplementation) and sarcopenia diagnostic parameters, namely low handgrip strength, appendicular lean mass (ALM), and gait speed. Additionally, multivariable Mendelian randomization (MVMR) was employed to assess the independent causal effects of these biomarkers. Replication analyses were subsequently performed using alternative datasets for sarcopenia diagnostic parameters. Meta-analyses were conducted to synthesize the results from both primary and replication TSMR analyses. Results The MR estimates derived from primary, multivariable, and replication analyses did not reveal significant causal associations between vitamin D-related biomarkers and sarcopenia diagnostic parameters. However, meta-analytic results indicated significant causal relationships between the absence of vitamin D deficiency and gait speed (β=0.001, 95% CI = 0.000 2-0.001 8, P=0.019) as well as low handgrip strength (OR=0.993, 95% CI=0.987-0.999, P=0.015), and between serum 25(OH)D levels and gait speed (β=0.015, 95% CI=0.004-0.027, P=0.009). Conclusion Maintaining optimal levels of serum 25-hydroxyvitamin D may help prevent the decline in gait speed, while the absence of vitamin D deficiency may also reduce the risk of developing low handgrip strength.

Key words: 25-hydroxyvitamin D, Sarcopenia, Mendelian randomization, Meta-analysis

中图分类号:

R151

晏师康, 李慧龙, 开地日艳·库日班江, 陈思敏, 陈亚琳, 杨蕾. 维生素D相关指标与肌少症诊断参数孟德尔随机化研究[J]. 华南预防医学, 2025, 51(9): 984-990.

YAN Shikang, LI Huilong, KAIDIRIYAN KURIBENJANG, CHEN Simin, CHEN Yalin, YANG Lei. Vitamin D-related biomarkers and sarcopenia diagnostic parameters: A Mendelian Randomization study[J]. South China Journal of Preventive Medicine, 2025, 51(9): 984-990.

参考文献

[1] Kirk B, Cawthon PM, Arai H, et al.The conceptual definition of sarcopenia: Delphi consensus from the global leadership initiative in sarcopenia (GLIS)[J]. Age Ageing, 2024, 53(3): 52-62.
[2] Petermann-Rocha F, Balntzi V, Gray SR, et al.Global prevalence of sarcopenia and severe sarcopenia: A systematic review and meta-analysis[J]. J Cachexia Sarcopenia Muscle, 2022, 13(1): 86-99.
[3] 高超,于普林. 老年人肌少症的研究现状和进展[J]. 中华老年医学杂志,2021,40(5):668-671.
[4] 崔华,王朝晖,吴剑卿,等. 老年人肌少症防控干预中国专家共识(2023)[J]. 中华老年医学杂志,2023,42(2):144-153.
[5] Kuwabara A, Matsumoto M, Hatamoto Y, et al.Vitamin D and muscle health: Insights from recent studies[J]. Curr Opin Clin Nutr Metab Care, 2024, 27(6): 499-506.
[6] Roh S, Kim KS.The relationship between vitamin D level and sarcopenia: Insights from a Korean population study[J]. Metabolism, 2024, 153: 155845.
[7] Jia S, Zhao W, Hu F, et al.Sex differences in the association of physical activity levels and vitamin D with obesity, sarcopenia, and sarcopenic obesity: A cross-sectional study[J]. BMC Geriatr, 2022, 22(1): 898-906.
[8] Gauzzi MC.Vitamin D-binding protein and multiple sclerosis: Evidence, controversies, and needs[J]. Mult Scler, 2018, 24(12): 1526-1535.
[9] Remelli F, Vitali A, Zurlo A, et al.Vitamin D deficiency and sarcopenia in older persons[J]. Nutrients, 2019, 11(12): 2861-2875.
[10] Mizuno T, Hosoyama T, Tomida M, et al.Influence of vitamin D on sarcopenia pathophysiology: A longitudinal study in humans and basic research in knockout mice[J]. J Cachexia Sarcopenia Muscle, 2022, 13(6): 2961-2973.
[11] Bouillon R, Manousaki D, Rosen C, et al.The health effects of vitamin D supplementation: Evidence from human studies[J]. Nat Rev Endocrinol, 2022, 18(2): 96-110.
[12] Chang MC, Choo YJ.Effects of whey protein, leucine, and vitamin D supplementation in patients with sarcopenia: A systematic review and meta-analysis[J]. Nutrients, 2023, 15(3): 521-533.
[13] Sha T, Wang Y, Zhang Y, et al.Genetic variants, serum 25-hydroxyvitamin D levels, and sarcopenia: A Mendelian randomization analysis[J]. JAMA Netw Open, 2023, 6(8): e2331558.
[14] Sanderson E, Glymour MM, Holmes MV, et al.Mendelian randomization[J]. Nat Rev Methods Primers, 2022, 2: 6.
[15] Revez JA, Lin T, Qiao Z, et al.Genome-wide association study identifies 143 loci associated with 25-hydroxyvitamin D concentration[J]. Nat Commun, 2020, 11(1): 1647-1659.
[16] Sun BB, Maranville JC, Peters JE, et al.Genomic atlas of the human plasma proteome[J]. Nature, 2018, 558(7708): 73-79.
[17] Jones G, Trajanoska K, Santanasto AJ, et al.Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women[J]. Nat Commun, 2021, 12(1): 654-665.
[18] Pei YF, Liu YZ, Yang XL, et al.The genetic architecture of appendicular lean mass characterized by association analysis in the UK biobank study[J]. Commun Biol, 2020, 3(1): 608-621.
[19] Burgess S, Small DS, Thompson SG.A review of instrumental variable estimators for Mendelian randomization[J]. Stat Methods Med Res, 2017, 26(5): 2333-2355.
[20] Burgess S, Bowden J, Fall T, et al.Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants[J]. Epidemiology, 2017, 28(1): 30-42.
[21] Ong JS, MacGregor S. Implementing MR-PRESSO and GCTA-GSMR for pleiotropy assessment in Mendelian randomization studies from a practitioner's perspective[J]. Genet Epidemiol, 2019, 43(6): 609-616.
[22] Sanderson E.Multivariable Mendelian randomization and mediation[J]. Cold Spring Harb Perspect Med, 2021, 11(2): a038984.
[23] Pinto Pereira SM, Garfield V, Norris T, et al.Linear and nonlinear associations between vitamin D and grip strength: A Mendelian randomization study in UK biobank[J]. J Gerontol A Biol Sci Med Sci, 2023, 78(8): 1483-1488.
[24] Annweiler C, Henni S, Walrand S, et al.Vitamin D and walking speed in older adults: Systematic review and meta-analysis[J]. Maturitas, 2017, 106: 8-25.
[25] Chen LK, Arai H, Assantachai P, et al.Roles of nutrition in muscle health of community-dwelling older adults: Evidence-based expert consensus from Asian Working Group for Sarcopenia[J]. J Cachexia Sarcopenia Muscle, 2022, 13(3): 1653-1672.
[26] 李想,傅伊铭,孙悦,等. 维生素D与老年肌肉减少症关系的研究进展[J]. 医学综述,2021,27(3):436-441.
[27] Abrams GD, Feldman D, Safran MR.Effects of vitamin D on skeletal muscle and athletic performance[J]. J Am Acad Orthop Surg, 2018, 26(8): 278-285.
[28] Prokopidis K, Giannos P, Katsikas Triantafyllidis K, et al.Effect of vitamin D monotherapy on indices of sarcopenia in community-dwelling older adults: A systematic review and meta-analysis[J]. J Cachexia Sarcopenia Muscle, 2022, 13(3): 1642-1652.
[29] Song Z, Pan T, Tong X, et al.The effects of nutritional supplementation on older sarcopenic individuals who engage in resistance training: A meta-analysis[J]. Front Nutr, 2023, 10: 1109789.
[30] Yoo JI, Chung HJ, Kim BG, et al.Comparative analysis of the association between various serum vitamin D biomarkers and sarcopenia[J]. J Clin Lab Anal, 2021, 35(9): e23946.
[31] Bollen SE, Bass JJ, Crossland H, et al.The association of vitamin D binding protein gene (GC) single nucleotide polymorphisms with skeletal muscle function and performance in master athletes[J]. Acta Physiol, 2022, 236: 365-367.
[32] Tsuprykov O, Chen X, Hocher CF, et al.Why should we measure free 25(OH) vitamin D[J]. J Steroid Biochem Mol Biol, 2018, 180: 87-104.
[33] Minelli C, Del Greco MF, van der Plaat DA, et al. The use of two-sample methods for Mendelian randomization analyses on single large datasets[J]. Int J Epidemiol, 2021, 50(5): 1651-1659.