Department of Nephrology, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, Jiangsu, China.
J Clin Pharmacol. 2023 Dec;63(12):1430-1437. doi: 10.1002/jcph.2332. Epub 2023 Oct 2.
This study is aimed at investigating the correlations of PCSK9 and LDLR gene polymorphisms as well as serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with atherosclerosis and lipid metabolism in patients on maintenance hemodialysis (HD). A single nucleotide polymorphism at the E670G locus of the PCSK9 gene and the rs688 locus of the LDLR gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. All study subjects' blood lipid (triglyceride [TG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]) concentrations and lipoprotein(a) and PCSK9 levels were measured. The differences in blood lipid levels between different genotypes of the E670G locus of the PCSK9 gene and the rs688 locus of the LDLR gene in patients on maintenance HD with atherosclerosis were compared. Patients on maintenance HD with atherosclerosis at the E670G locus of the PCSK9 gene AG + GG genotype had higher levels of TG, TC, LDL-C, and lipoprotein(a) than the AA genotype, and lower levels of HDL-C than the AA genotype. Patients on maintenance HD with atherosclerosis at the rs688 locus of the LDLR gene CT + TT genotype had higher levels of TG, TC, LDL-C, and lipoprotein(a) than the CC genotype, and lower levels of HDL-C than the CC genotype. Serum PCSK9 contents in patients on maintenance HD with atherosclerosis were positively correlated with lipid indices (TG, TC, LDL-C, and lipoprotein(a)) and carotid ultrasound indices (intima-media thickness and resistance index), and negatively correlated with HDL-C, maximum systolic blood flow velocity, and minimum diastolic blood flow velocity (all P < .05).
本研究旨在探讨载脂蛋白 B 代谢关键基因 PCSK9 和 LDLR 基因多态性及其血清前蛋白转化酶枯草溶菌素/κexin9 型（PCSK9）水平与维持性血液透析（HD）患者动脉粥样硬化及脂代谢的相关性。采用聚合酶链反应-限制性片段长度多态性分析方法检测 PCSK9 基因 E670G 位点和 LDLR 基因 rs688 位点单核苷酸多态性。检测所有研究对象的血脂（甘油三酯[TG]、总胆固醇[TC]、高密度脂蛋白胆固醇[HDL-C]和低密度脂蛋白胆固醇[LDL-C]）、脂蛋白（a）和 PCSK9 水平。比较不同基因型的载脂蛋白 B 代谢关键基因 PCSK9 基因 E670G 位点和 LDLR 基因 rs688 位点在维持性 HD 合并动脉粥样硬化患者的血脂水平差异。PCSK9 基因 E670G 位点 AG+GG 基因型维持性 HD 合并动脉粥样硬化患者的 TG、TC、LDL-C、脂蛋白（a）水平高于 AA 基因型，HDL-C 水平低于 AA 基因型。LDLR 基因 rs688 位点 CT+TT 基因型维持性 HD 合并动脉粥样硬化患者的 TG、TC、LDL-C、脂蛋白（a）水平高于 CC 基因型，HDL-C 水平低于 CC 基因型。维持性 HD 合并动脉粥样硬化患者的血清 PCSK9 含量与血脂指标（TG、TC、LDL-C、脂蛋白（a））及颈动脉超声指标（内膜-中层厚度和阻力指数）呈正相关，与 HDL-C、最大收缩期血流速度、最小舒张期血流速度呈负相关（均 P<0.05）。
