Li Cong, Feng Yu, Feng Lina, Li Mingquan
College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
Affiliated Hospital of the Changchun University of Chinese Medicine, Changchun, China.
Metab Brain Dis. 2024 Dec 27;40(1):78. doi: 10.1007/s11011-024-01448-y.
Some studies have shown an association between dyslipidemia and diabetic neuropathy (DN), but the genetic association has not been clarified. Therefore, the present study aimed to investigate the genetic causal association between dyslipidemia and DN through a Mendelian randomization (MR) approach. Genetic causal associations between total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) and DN were investigated by MR to provide a basis for the prevention and treatment of DN. Significant and independent single-nucleotide polymorphisms (SNPs) identified in genome-wide association studies were selected as instrumental variables (IVs) for MR analysis. Inverse variance weighted (IVW), MR‒Egger regression, weighted median (WME), simple mode (SM), and weighted mode (WM) methods were used to analyze causal associations. Heterogeneity and multiplicity tests were also performed and analyzed using the leave-one-out method to assess the stability of the results. Genetically predicted TC and DN (OR = 0.793, 95% CI = 0.655⁓0.961, P = 0.019) and LDL and DN (OR = 0.842, 95% CI = 0.711⁓0.998, P = 0.049) may be causally associated, but no causal associations were found between TG and DN (OR = 0.837, 95% CI = 0.631⁓1.111, P = 0.221) or between HDL and DN (OR = 1.192, 95% CI = 0.940⁓1.510, P = 0.149). TC and LDL may have genetic causal associations with DN, though no genetic causal associations were found for TG or HDL with DN. However, this study may have several limitations, and further clinical studies are needed to expand the sample size for future validation.
一些研究表明血脂异常与糖尿病神经病变（DN）之间存在关联，但遗传关联尚未明确。因此，本研究旨在通过孟德尔随机化（MR）方法探讨血脂异常与DN之间的遗传因果关联。通过MR研究总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL）和高密度脂蛋白胆固醇（HDL）与DN之间的遗传因果关联，为DN的防治提供依据。在全基因组关联研究中鉴定出的显著且独立的单核苷酸多态性（SNP）被选作MR分析的工具变量（IV）。采用逆方差加权（IVW）、MR-Egger回归、加权中位数（WME）、简单模式（SM）和加权模式（WM）方法分析因果关联。还使用留一法进行异质性和多重性检验并分析，以评估结果的稳定性。遗传预测的TC与DN（OR = 0.793，95%CI = 0.655⁓0.961，P = 0.019）以及LDL与DN（OR = 0.842，95%CI = 0.711⁓0.998，P = 0.049）可能存在因果关联，但未发现TG与DN之间（OR = 0.837，95%CI = 0.631⁓1.111，P = 0.221）或HDL与DN之间（OR = 1.192，95%CI = 0.940⁓1.510，P = 0.149）存在因果关联。TC和LDL可能与DN存在遗传因果关联，而TG或HDL与DN未发现遗传因果关联。然而，本研究可能存在一些局限性，需要进一步的临床研究扩大样本量以供未来验证。
