Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
Department of Life Science, Chinese Culture University, Taipei, Taiwan.
Lipids Health Dis. 2019 May 10;18(1):111. doi: 10.1186/s12944-019-1057-9.
Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses.
A total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies.
SNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01).
Our data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.
肝脂肪酶（HL，由 LIPC 编码）是一种主要由肝细胞合成和分泌的糖蛋白。先前的研究表明，HL 对胆固醇逆转运至关重要，并影响几种脂蛋白的代谢、组成和水平。在本研究中，我们通过亚组和中介分析研究了 LIPC（肝型脂肪酶）变体与循环和尿液生物标志物水平的关联。
使用 TaqMan 检测法对来自台湾的 572 名参与者进行了三种 LIPC 单核苷酸多态性（SNP）的基因分型。测量空腹血糖、血脂谱、炎症标志物、尿肌酐和 8-羟基脱氧鸟苷（8-OHdG）水平。使用卡方检验、2 样本 t 检验和方差分析（ANOVA）检验变量和基因型频率之间的差异。
SNP rs2043085 和 rs1532085 与尿液 8-OHdG 水平显著相关，而在分别进一步调整 HDL-C 或 TG 水平后，所有三种 SNP 与 TG 或 HDL-C 水平的相关性更为显著。亚组分析显示，LIPC SNP 与血清 TG、HDL-C 和尿液 8-OHdG 水平的相关性主要见于男性，而女性则不然。在不同肥胖状态的参与者中，LIPC SNP 与各种血脂水平的相关性存在差异。中介分析表明，TG 水平作为一种抑制物，掩盖了 LIPC 基因型与 HDL-C 水平之间的关联，尤其是在男性中（Sobel 检验，均 P<0.01）。
我们的数据显示，相互作用和抑制作用介导了 LIPC 变体的多效关联。LIPC SNP 的作用取决于性别、肥胖状态和 TG 水平。因此，我们的研究结果可以为心血管疾病高危人群的临床诊断提供一种方法。
