Li Yiming, Karppinen Jaro, Cheah Kathryn S E, Chan Danny, Sham Pak C, Samartzis Dino
Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
Eur Spine J. 2022 Mar;31(3):735-745. doi: 10.1007/s00586-021-06995-x. Epub 2021 Sep 25.
Modic changes (MC) on magnetic resonance imaging (MRI) have been associated with the development and severity of low back pain (LBP). The etiology of MC remains elusive, but it has been suggested that altered metabolism may be a risk factor. As such, this study aimed to identify metabolomic biomarkers for MC phenotypes of the lumbar spine via a combined metabolomic-genomic approach.
A population cohort of 3,584 southern Chinese underwent lumbar spine MRI. Blood samples were genotyped with single-nucleotide polymorphisms (SNP) arrays (n = 2,482) and serum metabolomics profiling using magnetic resonance spectroscopy (n = 757), covering 130 metabolites representing three molecular windows, were assessed. Genome-wide association studies (GWAS) were performed on each metabolite, to construct polygenic scores for predicting metabolite levels in subjects who had GWAS but not metabolomic data. Associations between predicted metabolite levels and MC phenotypes were assessed using linear/logistic regression and least absolute shrinkage and selection operator (LASSO). Two-sample Mendelian randomization analysis tested for causal relationships between metabolic biomarkers and MC.
20.4% had MC (10.6% type 1, 67.2% type 2, 22.2% mixed types). Significant MC metabolomic biomarkers were mean diameter of very-low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) particles and cholesterol esters/phospholipids in large LDL. Mendelian randomization indicated that decreased VLDL mean diameter may lead to MC.
This large-scale study is the first to address metabolomics in subject with/without lumbar MC. Causality studies implicate VLDL related to MC, noting a metabolic etiology. Our study substantiates the field of "spino-metabolomics" and illustrates the power of integrating metabolomics-genomics-imaging phenotypes to discover biomarkers for spinal disorders, paving the way for more personalized spine care for patients.
磁共振成像（MRI）上的Modic改变（MC）与腰痛（LBP）的发生和严重程度相关。MC的病因尚不清楚，但有人提出代谢改变可能是一个危险因素。因此，本研究旨在通过代谢组学-基因组学联合方法确定腰椎MC表型的代谢组学生物标志物。
对3584名中国南方人群进行腰椎MRI检查。对血液样本进行单核苷酸多态性（SNP）阵列基因分型（n = 2482），并使用磁共振波谱进行血清代谢组学分析（n = 757），评估了代表三个分子窗口的130种代谢物。对每种代谢物进行全基因组关联研究（GWAS），构建多基因评分以预测有GWAS数据但无代谢组学数据的受试者的代谢物水平。使用线性/逻辑回归和最小绝对收缩和选择算子（LASSO）评估预测的代谢物水平与MC表型之间的关联。两样本孟德尔随机化分析测试代谢生物标志物与MC之间的因果关系。
20.4%的人有MC（10.6%为1型，67.2%为2型，22.2%为混合型）。显著的MC代谢组学生物标志物是极低密度脂蛋白（VLDL）/低密度脂蛋白（LDL）颗粒的平均直径以及大LDL中的胆固醇酯/磷脂。孟德尔随机化表明VLDL平均直径减小可能导致MC。
这项大规模研究首次在有/无腰椎MC的受试者中进行代谢组学研究。因果关系研究表明VLDL与MC有关，提示存在代谢病因。我们的研究证实了“脊柱代谢组学”领域，并说明了整合代谢组学-基因组学-成像表型以发现脊柱疾病生物标志物的作用，为为患者提供更个性化的脊柱护理铺平了道路。
