Departments of Cardiology, Liuzhou People's Hospital, 8 Wenchang Road, Liuzhou, 545006, Guangxi, People's Republic of China.
Departments of Nephrology, Liuzhou People's Hospital, 8 Wenchang Road, Liuzhou, 545006, Guangxi, People's Republic of China.
BMC Nephrol. 2021 Jan 20;22(1):35. doi: 10.1186/s12882-020-02228-3.
While observational studies show an association between serum lipid levels and cardiovascular disease (CVD), intervention studies that examine the preventive effects of serum lipid levels on the development of CKD are lacking.
To estimate the role of serum lipid levels in the etiology of CKD, we conducted a two-sample mendelian randomization (MR) study on serum lipid levels. Single nucleotide polymorphisms (SNPs), which were significantly associated genome-wide with serum lipid levels from the GLGC and CKDGen consortium genome-wide association study (GWAS), including total cholesterol (TC, n = 187,365), triglyceride (TG, n = 177,861), HDL cholesterol (HDL-C, n = 187,167), LDL cholesterol (LDL-C, n = 173,082), apolipoprotein A1 (ApoA1, n = 20,687), apolipoprotein B (ApoB, n = 20,690) and CKD (n = 117,165), were used as instrumental variables. None of the lipid-related SNPs was associated with CKD (all P > 0.05).
MR analysis genetically predicted the causal effect between TC/HDL-C and CKD. The odds ratio (OR) and 95% confidence interval (CI) of TC within CKD was 0.756 (0.579 to 0.933) (P = 0.002), and HDL-C was 0.85 (0.687 to 1.012) (P = 0.049). No causal effects between TG, LDL-C- ApoA1, ApoB and CKD were observed. Sensitivity analyses confirmed that TC and HDL-C were significantly associated with CKD.
The findings from this MR study indicate causal effects between TC, HDL-C and CKD. Decreased TC and elevated HDL-C may reduce the incidence of CKD but need to be further confirmed by using a genetic and environmental approach.
虽然观察性研究表明血清脂质水平与心血管疾病（CVD）之间存在关联，但缺乏研究血清脂质水平对慢性肾脏病（CKD）发展的预防作用的干预研究。
为了评估血清脂质水平在 CKD 发病机制中的作用，我们对血清脂质水平进行了两样本孟德尔随机化（MR）研究。来自 GLGC 和 CKDGen 联盟全基因组关联研究（GWAS）的与血清脂质水平显著相关的单核苷酸多态性（SNP），包括总胆固醇（TC，n=187365）、甘油三酯（TG，n=177861）、高密度脂蛋白胆固醇（HDL-C，n=187167）、低密度脂蛋白胆固醇（LDL-C，n=173082）、载脂蛋白 A1（ApoA1，n=20687）、载脂蛋白 B（ApoB，n=20690）和 CKD（n=117165），被用作工具变量。没有一个脂质相关的 SNP 与 CKD 相关（均 P>0.05）。
MR 分析从遗传上预测了 TC/HDL-C 与 CKD 之间的因果关系。TC 在 CKD 中的比值比（OR）和 95%置信区间（CI）为 0.756（0.579 至 0.933）（P=0.002），HDL-C 为 0.85（0.687 至 1.012）（P=0.049）。没有观察到 TG、LDL-C、ApoA1 和 ApoB 与 CKD 之间的因果关系。敏感性分析证实，TC 和 HDL-C 与 CKD 显著相关。
这项 MR 研究的结果表明 TC、HDL-C 与 CKD 之间存在因果关系。TC 降低和 HDL-C 升高可能会降低 CKD 的发病率，但需要通过遗传和环境方法进一步证实。
