Supplementary Material for: Effects of Gene Variants Controlling Vitamin D Metabolism and Serum Levels on Hepatic Steatosis

Background/Aims: Common genetic variations in vitamin D metabolism are associated with liver stiffness. Whether these genes are implicated in hepatic steatosis remains unclear. Here we aimed to analyse the association of common vitamin D pathway gene variants with liver steatosis. Methods: Liver steatosis was assessed non-invasively in 241 patients with chronic liver conditions by controlled attenuation parameter (CAP). The following polymorphisms were genotyped using TaqMan assays: group-specific component (GC) rs7041, 7-dehydrocholesterol reductase (DHCR7) rs12785878, cytochrome P450 2R1 (CYP2R1) rs10741657, vitamin D receptor (VDR) rs7974353. Chemiluminescence immunoassay determined serum 25-hydroxyvitamin D (25(OH) D) concentrations. Results: Vitamin D deficiency (defined by 25(OH)D concentrations <20 ng/mL) occurred in 66% of patients. Median CAP was 296 (100–400) dB/m. Patients with advanced steatosis (CAP ≥280 dB/m) had significantly (p = 0.033) lower 25(OH)D levels as compared to patients with CAP <280 dB/m. Moreover, the rare allele [T] in GC rs7041 was significantly (p = 0.018) associated with higher 25(OH)D levels in patients with CAP <280 dB/m. However, GC, DHCR7, CYP2R1, and VDR polymorphisms were not related to liver steatosis and obesity traits. Conclusions: Higher CAP values are associated with low serum 25(OH)D concentrations but not with common vitamin D pathway gene variants.

背景与目的：维生素D代谢相关常见遗传变异与肝脏硬度存在关联，但此类基因是否参与肝脏脂肪变性的发生发展仍有待阐明。本研究旨在探讨维生素D代谢通路常见基因变异与肝脏脂肪变性的相关性。方法：本研究通过受控衰减参数（controlled attenuation parameter, CAP）对241例慢性肝病患者的肝脏脂肪变性进行无创评估。采用TaqMan检测法对以下多态性位点进行基因分型：组特异性组分（group-specific component, GC）rs7041、7-脱氢胆固醇还原酶（7-dehydrocholesterol reductase, DHCR7）rs12785878、细胞色素P450 2R1（cytochrome P450 2R1, CYP2R1）rs10741657及维生素D受体（vitamin D receptor, VDR）rs7974353。采用化学发光免疫分析法检测血清25-羟维生素D（25(OH)D）浓度。结果：66%的患者存在维生素D缺乏（定义为血清25(OH)D浓度<20 ng/mL）。患者的CAP中位数为296（100–400）dB/m。与CAP<280 dB/m的患者相比，重度脂肪变性患者（CAP≥280 dB/m）的血清25(OH)D水平显著更低（p=0.033）。此外，在CAP<280 dB/m的患者中，GC rs7041位点的罕见等位基因[T]与较高的血清25(OH)D水平显著相关（p=0.018）。然而，GC、DHCR7、CYP2R1及VDR基因多态性与肝脏脂肪变性及肥胖表型均无关联。结论：较高的CAP值与较低的血清25(OH)D浓度相关，但与维生素D代谢通路常见基因变异无关。