Single-nucleotide polymorphisms (SNPs) of apolipoprotein C3 (APOC3) play important role in lipid metabolism, and dyslipidemia underlies nonalcoholic fatty liver disease (NAFLD). But the correlation of serum lipidomics, APOC3 SNPs, and NAFLD remains limited understood. Enrolling thirty-four biopsy-proven NAFLD patients from Tianjin, Shanghai, Fujian, we investigated their APOC3 genotype and serum lipid profile by DNA sequencing and ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. Scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was then performed to reveal the role of lipidomics-affecting APOC3 SNPs in NAFLD-specific pathological alterations. Here, we reported that APOC3 SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) intimately correlated to serum lipidomics in NAFLD patients. A allele instead of G allele at rs2070667, which dominated the SNPs underlying lipidomic alteration, exhibited downregulatory effect on triacylglycerols (TGs: TG 54 : 7, TG 54 : 8, and TG 56 : 9) containing polyunsaturated fatty acid (PUFA). Moreover, subjects with low-level PUFA-containing TGs were predisposed to high-grade lobular inflammation (TG 54 : 7, and ; TG 54 : 8, and P =0.016; TG 56 : 9, and ). The significant correlation of APOC3 rs2070667 and inflammation grading [G/G vs. G/A+A/A: 0.00 (0.00 and 1.00) vs. 1.50 (0.75 and 2.00), ] further confirmed its pathological action on the basis of lipidomics-impacting activity. These findings suggest an inhibitory effect of A allele at APOC3 rs2070667 on serum levels of PUFA-containing TGs, which are associated with high-grade lobular inflammation in NAFLD patients.

中文翻译：

---

APOC3 rs2070667与非酒精性脂肪肝疾病中的血清甘油三酸酯谱和肝炎症相关

载脂蛋白C3（APOC3）的单核苷酸多态性（SNPs）在脂质代谢中起重要作用，而血脂异常是非酒精性脂肪肝病（NAFLD）的基础。但是，血清脂质组学，APOC3 SNP和NAFLD的相关性仍然有限。我们收集了来自天津，上海，福建的34名经活检证实的NAFLD患者，分别通过DNA测序和超高效液相色谱-串联质谱法（UPLC-MS / MS）研究了他们的APOC3基因型和血清脂质谱。然后对肝细胞脂肪变性，球囊扩张，小叶炎症和肝纤维化进行评分，以揭示影响脂质组学的APOC3的作用NAFLD特定病理改变中的SNP。在这里，我们报道了APOC3 SNP（rs4225，rs4520，rs5128，rs2070666和rs2070667）与NAFLD患者的血清脂质组学密切相关。rs2070667的一个等位基因代替G等位基因，它主导着脂质组学改变的SNP，对含有多不饱和脂肪酸（PUFA）的三酰甘油（TGs：TG 54：7，TG 54：8和TG 56：9）表现出下调作用。此外，患有低水平PUFA TG的受试者易患高级别小叶炎症（TG 54：7， 和 ; TG 54：8和P  = 0.016; TG 56：9 和 ）。APOC3 rs2070667与炎症等级显着相关[G / G与G / A + A / A：0.00（0.00和1.00）与1.50（0.75和2.00），]基于脂质组学影响活性进一步证实了其病理作用。这些发现表明A等位基因在APOC3 rs2070667处对血清中含有PUFA的TG的抑制作用，这与NAFLD患者中的高度小叶炎症有关。