Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China.
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Ann Nutr Metab. 2022;78(2):61-72. doi: 10.1159/000522193. Epub 2022 Jan 31.
Vitamin D-binding protein (VDBP) is correlated with nonalcoholic fatty liver disease (NAFLD) through the biological functions of regulating plasma vitamin D (VD) level and the inflammatory process.
This study aims to investigate the effects of VD level and VDBP gene polymorphisms on the risk of NAFLD in a Chinese population.
Plasma 25-hydroxyvitamin D3 levels were measured and seven VDBP candidate genetic variants (rs222020, rs2282679, rs4588, rs1155563, rs7041, rs16847024, rs3733359) were genotyped among participants in this case-control study. The control group was frequency-matched to the NAFLD case group by age and gender. Correlation analysis and multiple linear regressions were used to screen determinants of 25-hydroxyvitamin D3 levels. Multivariable unconditional logistic regression was performed to estimate odds ratio (OR) and 95% confidence interval (95% CI). The prediction capability of models containing independent factors was estimated by the area under the receiver operating characteristic curve and Hosmer-Lemeshow test.
Age, body mass index, and triacylglycerol were independent factors influencing VD levels. Participants with low VD levels had significantly higher prevalence of NAFLD compared to subjects with normal VD levels (p < 0.001). A low VD level contributed to increased the risk of NAFLD, independent of metabolic factors known to affect VD levels (adjusted OR = 2.282, 95% CI = 1.422-3.661, p = 0.001). Logistic regression analysis showed that individuals carrying rs7041-G allele had a significantly decreased the risk of NAFLD occurrence compared to T allele (additive model: adjusted OR = 0.814, 95% CI = 0.713-0.929, p = 0.002; codominant model: adjusted OR = 0.623, 95% CI = 0.449-0.866, p = 0.005), after adjusting for age, gender, and overweight. Stratification by multiple metabolic disorders did not alter this relationship. Moreover, we developed a simple model including age, gender, metabolic disorders, and VDBP single nucleotide polymorphism (SNP) to assess NAFLD risk, an AUC of which being 0.817, significantly higher than the model not included VDBP SNP, with Hosmer-Lemeshow test fitting well (p = 0.182).
Low plasma VD levels may increase susceptibility to NAFLD, while rs7041-G allele in VDBP contributed to a decreased NAFLD risk among Chinese population. The VDBP variant significantly improved the capability for NAFLD risk assessment, which could be used for early screening and management of NAFLD.
维生素 D 结合蛋白（VDBP）通过调节血浆维生素 D（VD）水平和炎症过程与非酒精性脂肪性肝病（NAFLD）相关。
本研究旨在探讨 VD 水平和 VDBP 基因多态性对中国人群 NAFLD 发病风险的影响。
在这项病例对照研究中，测量了参与者的血浆 25-羟维生素 D3 水平，并对 7 个 VDBP 候选遗传变异（rs222020、rs2282679、rs4588、rs1155563、rs7041、rs16847024、rs3733359）进行了基因分型。对照组按年龄和性别与 NAFLD 病例组进行频率匹配。使用相关分析和多元线性回归筛选 25-羟维生素 D3 水平的决定因素。采用多变量非条件逻辑回归估计比值比（OR）和 95%置信区间（95%CI）。通过受试者工作特征曲线下面积和 Hosmer-Lemeshow 检验评估包含独立因素的模型的预测能力。
年龄、体重指数和三酰甘油是影响 VD 水平的独立因素。与 VD 水平正常的受试者相比，VD 水平较低的患者 NAFLD 的患病率显著更高（p<0.001）。低 VD 水平与已知影响 VD 水平的代谢因素无关，可增加 NAFLD 的发病风险（调整 OR=2.282，95%CI=1.422-3.661，p=0.001）。逻辑回归分析显示，与 T 等位基因相比，携带 rs7041-G 等位基因的个体发生 NAFLD 的风险显著降低（加性模型：调整 OR=0.814，95%CI=0.713-0.929，p=0.002；显性模型：调整 OR=0.623，95%CI=0.449-0.866，p=0.005），校正年龄、性别和超重因素后。多代谢紊乱的分层并未改变这种关系。此外，我们建立了一个包含年龄、性别、代谢紊乱和 VDBP 单核苷酸多态性（SNP）的简单模型来评估 NAFLD 风险，其 AUC 为 0.817，显著高于不包含 VDBP SNP 的模型，Hosmer-Lemeshow 检验拟合良好（p=0.182）。
低血浆 VD 水平可能增加 NAFLD 的易感性，而 VDBP 中的 rs7041-G 等位基因可降低中国人群的 NAFLD 风险。VDBP 变异显著提高了 NAFLD 风险评估的能力，可用于 NAFLD 的早期筛查和管理。
